Extracorporeal Blood Processing Apparatus And Methods With Pressure Sensing

ABSTRACT

This invention provides an apparatus and method for controlling a fluid separation system, preferably a blood apheresis system, by sensing fluid pressure and comparing the sensed fluid pressure to a threshold value.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/530,131, filed Sep. 8, 2006; which is a division of U.S. patentapplication Ser. No. 10/681,035, filed Oct. 8, 2003 now U.S. Pat. No.7,169,352; which is a continuation-in-part of U.S. application Ser. No.09/746,987, filed Dec. 22, 2000, now issued U.S. Pat. No. 6,899,691;which claims the benefit of U.S. Provisional Application No. 60/171,932filed Dec. 22, 1999.

FIELD OF THE INVENTION

The present invention generally relates to the field of extracorporealblood processing and, more particularly, to methods and apparatus whichmay be incorporated into an automated apheresis system for bloodcomponent collection or therapy.

BACKGROUND OF THE INVENTION

One type of extracorporeal blood processing is an apheresis procedure inwhich blood is removed from a donor or patient, directed to a bloodcomponent separation device (e.g., centrifuge), and separated intovarious blood component types (e.g., red blood cells, white blood cells,platelets, plasma) for collection or therapeutic purposes. One or moreof these blood component types are collected (e.g., for transfusionpurposes), while the remainder is returned to the donor or patient. Anexample of an apheresis system is that disclosed in U.S. Pat. No.6,319,471, incorporated herein by reference to the extent notinconsistent herewith.

A number of factors affect the commercial viability of an apheresissystem. One factor relates to the operator of the system, specificallythe time and/or expertise required of an individual to prepare andoperate the apheresis system. For instance, reducing the time requiredby the operator to load and unload the disposables, as well as thecomplexity of these actions, can increase productivity and/or reduce thepotential for operator error. Moreover, reducing the dependency of thesystem on the operator may lead to reductions in operator errors and/orto reductions in the credentials desired/required for the operators ofthese systems.

Donor-related factors may also impact the commercial viability of anapheresis system and include donor convenience and donor comfort. Forinstance, donors typically have only a certain amount of time, which maybe committed to visiting a blood component collection facility for adonation. Consequently, once at the collection facility the amount ofthe donor's time, which is actually spent collecting blood components,is another factor which should be considered. This also relates to donorcomfort in that many view the actual collection procedure as beingsomewhat discomforting in that at least one and sometimes two accessneedles are in the donor throughout the procedure.

Performance-related factors continue to affect the commercial viabilityof an apheresis system as well. Performance may be judged in terms ofthe “collection efficiency” of the apheresis system, which may in turnreduce the amount of donation time and thus increase donor convenience.The “collection efficiency” of a system may of course be gauged in avariety of ways, such as by the amount of a particular blood componenttype, which is collected in relation to the number of this bloodcomponent type, which passes through the apheresis system. Performancemay also be evaluated based upon the effect, which the apheresisprocedure has on the various blood component types. For instance, it isdesirable to minimize the adverse effects on the blood component typesas a result of the apheresis procedure (e.g., limit hemolysis andplatelet activation).

A particularly important performance-related factor involves the controlof the access or draw pressure of the blood being drawn from the donoror patient. Properly maintained access/draw pressures contribute to thereduction of donation times and the minimization of donor/patientdiscomfort. Also, certain access/draw pressure conditions signify noflow or improper flow characteristics, which should be addressed by anoperator. For example, it is well known that the access/draw needle maybecome improperly seated or blocked within the donor/patient accesssite. Access/draw pressures sensed by the apheresis system can beinterpreted as indicating such a problem and then activating an alarmfor operator intervention and/or pump controls such as pump slowing orstoppage.

SUMMARY OF THE INVENTION

The present invention generally relates to extracorporeal bloodprocessing. Since each of the various aspects of the present inventionmay be incorporated into an apheresis system (e.g., whether for bloodcomponent collection in which “healthy” cells or other components areremoved from the blood or for therapeutic purposes in which “unhealthy”cells or other components are removed from the blood), the presentinvention will be described in relation to this particular application.However, at least certain of the aspects of the present invention may besuited for other extracorporeal blood processing applications and suchare within the scope of the present invention.

An apheresis system, which may embody one or more aspects of the presentinvention generally, includes a blood component separation device (e.g.,a membrane-based separation device, or a rotatable centrifuge element,such as a rotor, which provides the forces required to separate bloodinto its various blood component types (e.g., red blood cells, whiteblood cells, platelets, and plasma)). In one embodiment, the separationdevice includes a channel, which receives a blood processing vessel.Typically, a healthy human donor or a patient suffering from some typeof illness (hereafter, both collectively referred to as a donor/patient)is fluidly interconnected with the blood processing vessel by anextracorporeal tubing circuit, and preferably the blood processingvessel and extracorporeal tubing circuit collectively define a closed,sterile system. When the fluid interconnection is established, blood maybe extracted from the donor/patient and directed to the blood componentseparation device such that at least one type of blood component may beseparated and removed from the blood, either for collection or fortherapy.

One aspect of the present invention relates to improved automatedpressure monitoring and alarm handling in extracorporeal bloodprocessing applications.

Another aspect is improving the automated responses of an extracorporealblood processing device to certain pressure conditions.

This invention provides a method for controlling a fluid separationsystem comprising a three-level alarm system. The fluid separationsystem is preferably a blood apheresis system and preferably comprises aleukocyte reduction chamber.

The first-level alarm condition is triggered in response to a pressuredrop in the system to less than or equal to a specified system pressure.A system pressure is the fluid pressure in at least one portion of thesystem. Preferably the relevant pressure for triggering a first-levelalarm is the system pressure at the inlet pump. In one embodiment, thefirst alarm condition comprises pausing the fluid flow in at lest aportion of the system for a specific delay time. In an exemplaryembodiment, the first alarm condition comprises pausing the fluid flowin at least a portion of the system for a delay time of about 2 secondsto about 6 seconds. Preferably, in a blood apheresis system comprising aleukocyte reduction chamber, the platelet pump is not paused, as thiswill allow fluid flow to be maintained through the leukocyte reductionchamber.

A second-level alarm condition is triggered in response to a specifiednumber of said pressure drops within a specified period. (Optionally, ifplasma and platelet collection has been completed, instead of triggeringa second-level alarm condition, a third-level alarm condition withshut-down of all pumps may be triggered instead.)

The second-level alarm condition comprises reducing the flow rate of thefluid in the system. Preferably the alarm conditions trigger a visibleand/or audible alarm, and preferably the second-level alarm conditiontriggers a continuous alarm. A “continuous” alarm as used in thiscontext may be intermittent. The second-level alarm condition persistsuntil operator intervention. The operator may correct the problem, e.g.,by adjusting needle position or increasing pressure in the pressurecuff, and return the system to normal operation, or if the problemcannot be resolved, the operator may shut down the system and terminatethe session. The operator also has the option of slowing down the flowrate. Typically, the system comprises a flow control button by which theoperator can slow the flow rate by 5 ml/min decrements. This is useful,for example, when second-level alarms are repeatedly triggered by aparticular patient, and the operator decides this patient cannot supportthe higher flow rates, for example, because the patient is not willingto operate a squeeze ball to enhance pressure of the blood entering theneedle.

An advantage of these alarm levels is to permit flow through theleukocyte reduction chamber to continue when the pressure drop is causedby a non-serious, self-resolving or easily-correctable condition such asmisalignment of system components. For example, the needle in thepatient may be misaligned, the pressure cuffs may be improperlyadjusted, or the patient's blood pressure may have fallen.

Preferably the specified number of pressure drops is between about twoand about five, more preferably about three. Preferably the specifieddelay time is between about 2 and about 6 seconds, and more preferablyabout 5 seconds.

The specified period in which pressure drops are counted is preferablybetween about 1 and about 10 minutes, preferably about 5 minutes.

Preferably the specified system pressure is between about −100 and about−250 mmHg.

The method also comprises returning the flow rate in the system tonormal if pressure in the system rises above a specified alarm-disablingpressure which is preferably between about 0 and about −150 mmHg andmore preferably about −50 mmHg.

The second-level alarm condition preferably reduces the flow rate in thesystem to a level low enough to prevent triggering of a furtherfirst-level alarm condition. Preferably this flow rate is about one-halfthe normal flow rate in the system. Normal flow rates in apheresissystems are known to the art.

The second-level alarm condition is indefinite in duration and must beterminated by an operator by shutting down the system, correcting theproblem causing the pressure drop and returning the flow rate to normal,or the operator can also choose to slow the flow rate as discussedabove, e.g., in 5 ml/min decrements.

The specified system pressure generally is not directly sensed at apressure sensor. The pressure registered at the sensor is affected bycertain system parameters. Selected system parameters are therefore usedto calculate a sensor pressure, which will trigger a first-level alarm.This calculated sensor pressure is based on a specified system pressureand selected system parameters including inlet pump hematocrit, ratio ofanticoagulant to whole blood in an inlet line of the system duringplatelet and plasma collection, inlet pump flow rate, and donorhematocrit, a configuration specified system pressure, the flow rate inthe inlet tubing line, the hematocrit in the inlet tubing line, the flowrate in the needle and the hematocrit in the needle.

In one embodiment, the sensor pressure, which triggers the first-levelalarm is calculated using the formula:specified sensor pressure=Config+75−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n));where Config is a configuration specified system pressure (mmHg.),Q_(in) is the flow rate in the inlet tubing line (ml/min.); H_(in) isthe Hematocrit in the inlet tubing line; Q_(n) is the flow rate in theneedle (ml/min.); and H_(n) is the Hematocrit in the needle.Alternatively, the sensor pressure which triggers the first-level alarmmay be calculated using the formula:specified sensor pressure=Config+75−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H _(n));where Config is a configuration specified system pressure (mmHg.),Q_(in) is the flow rate in the inlet tubing line (ml/min.); H_(in) isthe Hematocrit in the inlet tubing line; Q_(n) is the flow rate in theneedle (ml/min.); and H_(n) is the Hematocrit in the needle.

During a first-level alarm condition, if the pressure in the systemrises to greater than or equal to a specified first-levelalarm-disabling system pressure, the first-level alarm condition will bedisabled and flow rates in the system will return to normal. Preferablythe specified first-level alarm-disabling system pressure is betweenabout 0 and about −150 mmHg, more preferably about −50 mmHg.

The method also comprises triggering a third alarm condition if systempressure fails to rise to the specified first-level alarm disablingsystem pressure.

This invention also provides a method for controlling the flow rate ofreturn of fluid to a fluid source in a fluid separation process whereincomponents have been separated from the fluid. Preferably the fluidseparation process is a blood apheresis process, more preferably asingle-needle blood apheresis process, which uses the same needle toremove blood from the donor and return it to the donor.

This method comprises specifying a system return-flow alarm-triggeringpressure, and when pressure of the system return flow is higher than orequal to this pressure, triggering a return-flow alarm which stops thereturn flow pump and preferably sounds an audible alarm and/or displaysa visible alarm. The sensor pressure, which triggers the return-flowalarm is preferably measured at the same location as the sensor pressurewhich triggers the first-level alarm, just upstream of the inlet pump.Again, the sensor pressure, which triggers the return-flow alarm isgenerally not the same as the specified system return-flowalarm-triggering pressure because the value shown by the sensor is notthe same as the pressure in the system. This sensor pressure fortriggering the return-flow alarm may be calculated using the specifiedsystem return-flow alarm-triggering pressure and selected systemparameters including return needle flow rate, return needle hematocrit,a configuration specified system pressure, the flow rate in the inlettubing line, the hematocrit in the inlet tubing line, the flow rate inthe needle and the hematocrit in the needle. Preferably the sensorpressure for triggering the return-flow alarm condition is calculatedusing the formula:specified sensor pressure=Config−50−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n));where Config is a configuration specified system pressure (mmHg), Q_(in)is the flow rate in the inlet tubing line (ml/min.); H_(in) is theHematocrit in the inlet tubing line; Q_(n) is the flow rate in theneedle (ml/min.); and H_(n) is the Hematocrit in the needle.Alternatively, the sensor pressure for triggering the return-flow alarmcondition is calculated using the formula:specified sensor pressure=Config−50−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H _(n));where Config is a configuration specified system pressure (mmHg), Q_(in)is the flow rate in the inlet tubing line (ml/min.); H_(in) is theHematocrit in the inlet tubing line; Q_(n) is the flow rate in theneedle (ml/min.); and H_(n) is the Hematocrit in the needle.

The specified system return-flow alarm-triggering pressure is preferablybetween about 100 and about 310 mmHg.

This invention also provides a fluid separation control systemcomprising: pumps for moving fluid through said system; a fluid pressuremonitoring device for sensing fluid pressures in said system andgenerating pressure signals in response to said sensed pressures; aprocessor for receiving said pressure signals and generatingalarm-triggering signals in response thereto; an audible and/or visiblealarm triggered by said alarm-triggering signals; and a flow controllertriggered by said alarm-triggering signals; wherein said processor isprogrammed to compare said sensed pressures with system pressures andgenerate a first-level alarm-triggering signal when said sensedpressures are less than or equal to a first-level alarm-triggeringsensor pressure; wherein said first-level alarm-triggering signal causessaid flow controller to pause fluid flow in some of said pumps for aspecified delay time; wherein said processor is programmed to count thenumber of first-level alarm-triggering signals generated within aspecified period and generate a second-level alarm-triggering signalwhen a specified number of such first-level alarm-triggering signalshave been generated within said specified period; and wherein saidsecond-level alarm-triggering signal causes said flow controller to slowdown fluid flow rate in said system.

The fluid-pressure monitoring device can be any pressure sensor known tothe art. The processor can be any computer processor known to the art,including a personal computer; the alarms can be audible such as bells,buzzers, electronically-generated sounds, and/or visual displays, e.g.,on a computer monitor, and other alarms known to the art. Theflow-controller can comprise switches, valves, pumps, and othercomponents known to the art for controlling fluid flow.

The alarm is responsive to the first-level alarm-triggering signal, andresponds by sounding an audible alarm and/or displaying a visible alarm.The alarm responds to the second-level alarm-triggering signal bycontinuously sounding an audible alarm and/or continuously displaying avisible alarm. As stated above, the “continuous” alarm can also beintermittent. The second-level alarm is indefinite in duration and doesnot cease until operator intervention terminates the second-level alarmcondition.

First-level alarm-triggering sensor pressures are calculated asdiscussed above.

The processor is preferably also programmed to generate a first-levelalarm-disabling signal if the sensed pressure rises to a value greaterthan or equal to a specified first-level alarm-disabling sensor pressurewithin the specified delay time, and the flow controller responds to thefirst-level alarm-disabling signal by causing pumps which had beenpaused to resume pumping, and causing any alarm which as been soundingor displayed to cease.

The specified first-level alarm-disabling sensor pressure may becalculated using system parameters as described above.

The processor is preferably also programmed to generate a third-levelalarm-triggering signal if the sensed pressure does not rise to a valuegreater than or equal to the specified first-level alarm-disablingsensor pressure within the specified delay time. The third-level alarmshuts down all pumps in the system and preferably also sounds an audiblealarm and/or displays a visible alarm.

The fluid separation system is preferably a blood apheresis systemcomprising a leukocyte reduction chamber, and preferably the flowcontroller does not pause fluid flow through the leukocyte reductionchamber in response to the first-level alarm-triggering signal.

The flow controller slows the flow rate in response to the second-levelalarm-triggering signal to a rate low enough to prevent triggering afurther first-level alarm condition, preferably to about one-half normalrate.

The control system may also comprise a process monitor for assessingcompleteness of collection of platelets and plasma; said processor beingin signal communication with said process monitor, and being programmedto trigger a second-level alarm condition only if collection ofplatelets and plasma is incomplete.

This invention also provides a fluid separation control systemcomprising a pump for returning fluid to a fluid source, said controlsystem comprising: a fluid pressure monitoring device for sensing returnfluid pressures in said system and generating return pressure signals inresponse to said sensed return fluid pressures; a processor forreceiving said return fluid pressure signals and generating areturn-alarm-triggering signal in response thereto; a flow controllertriggered by said return-alarm-triggering signal; wherein said processoris programmed to compare said sensed pressures with system returnpressures and generate a return alarm-triggering signal when said sensedpressures are greater than or equal to a specified system returnalarm-triggering pressure; wherein said return alarm-triggering signalcauses said flow controller to stop all pumps. The control system mayalso comprise an alarm responsive to said return alarm-triggeringsignal, which sounds an audible alarm or displays a visible alarm.Preferably the control system is a blood apheresis system.

In one embodiment the present invention provides a method forcontrolling a fluid separation system comprising the steps of: (1)triggering a first-level alarm condition in response to a pressure dropto less than or equal to a specified system pressure, said first alarmcondition comprising pausing fluid flow in at least a portion of saidsystem for a specified delay time; and (2) triggering a second alarmcondition in response to a specified number of said pressure dropswithin a specified period, said second alarm condition comprisingreducing flow rate of fluid in said system. Optionally, this method ofthe present invention may further comprise the step of triggering athird alarm condition in response to failure of pressure in the systemto rise to a specified first-level alarm-disabling pressure in thesystem. In another embodiment, the present invention comprises a methodfor controlling an apheresis system comprising the steps of: (1)triggering a first alarm condition in response to a specified pressuredrop to less than or equal to a specified pressure in the system, saidfirst alarm condition comprising pausing fluid flow in at least aportion of said system for a specified delay time; (2) if plasma andplatelet collection is incomplete, triggering a second-level alarmcondition in response to a specified number of said specified pressuredrops within a specified period, said second alarm condition comprisingreducing flow rate of fluid in said system; and (3) if plasma andplatelet collection is complete, triggering a third-level alarmcondition in response to a selected number of said selected pressuredrops within a specified period, said third-level alarm conditioncomprising stopping all pumps. In yet another embodiment, the presentinvention provides a method for controlling flow rate of return of fluidto a fluid source in a fluid separation process wherein components havebeen separated from said fluid, said method comprising the step ofspecifying a system return-flow alarm-triggering pressure, and whenpressure of said return flow in the system is higher than or equal tosaid specified pressure, triggering a return-flow alarm.

The foregoing and other features of the present invention will befurther illuminated in the following detailed description read inconjunction with the accompanying drawings, which are described brieflybelow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of one embodiment of an extracorporealsystem.

FIGS. 2A-2B illustrate an extracorporeal tubing circuit, cassetteassembly, and bag assemblies of the system of FIG. 1.

FIG. 2C illustrates an alternative extracorporeal tubing circuit and bagassemblies of an extracorporeal system usable in conjunction with thepresent invention.

FIG. 3 is a front view of a pump/valve/sensor assembly for the system ofFIG. 1.

FIGS. 4A-4B are cross-sectional side views of first and second pressuresensing modules of the extracorporeal tubing circuit of FIGS. 2A-2Bcoupled with corresponding pressure sensors of the pump/valve/sensorassembly of FIGS. 1 and 3.

FIG. 5 is an isometric view of the channel assembly and a portion of theextracorporeal tubing circuit of the system of FIG. 1.

FIG. 6 is a top view of the channel housing from the channel assembly ofFIG. 5.

FIG. 7 is a “master screen” for the computer graphics interface of theapheresis system of FIG. 1.

FIG. 8 is a “run screen” for the computer graphics interface of theapheresis system of FIG. 1.

FIG. 9 is one embodiment of a “warning screen” for the computer graphicsinterface of the apheresis system of FIG. 1.

FIG. 10 is an “alarm screen” for the warning screen of FIG. 9.

FIG. 11 is a flow diagram showing a preferred embodiment of thethree-level alarm system of this invention.

FIG. 12 is a block diagram showing components of a fluid separationcontrol system of this invention for triggering three alarm levels.

DETAILED DESCRIPTION

The present invention will be described in relation to the accompanyingdrawings, which assist in illustrating the pertinent features thereof.Generally, the present invention relates to improvements in a bloodapheresis system. However, certain of these improvements may beapplicable to other extracorporeal blood processing applications andsuch are within the scope of the present invention as well.

A blood apheresis system 2 such as is schematically illustrated in FIG.1 allows for a continuous blood component separation process. Generally,whole blood is withdrawn from a donor/patient 4 and is provided to ablood component separation device 6 where the blood is separated intothe various component types and at least one of these blood componenttypes is removed from the device 6. These separated blood components maythen be collected for subsequent use by transfusion to another patientor may undergo a therapeutic treatment and/or may be returned to thedonor/patient 4.

In a presently preferred embodiment of the blood apheresis system 2 asshown and described in all of the attached drawings, blood is withdrawnfrom the donor/patient 4 and directed as shown in FIG. 1 through adisposable set 8 which includes an extracorporeal tubing circuit 10 anda blood processing vessel 352 and which defines a completely closed andsterile system. The disposable set 8 is mounted in and/or on the bloodcomponent separation device 6 which includes a pump/valve/sensorassembly 1000 for interfacing with the extracorporeal tubing circuit 10,and a channel assembly 200 for interfacing with the disposable bloodprocessing vessel 352.

The channel assembly 200 includes a channel housing 204 which isrotatably interconnected with a rotatable centrifuge rotor assembly 568which provides the centrifugal forces required to separate blood intoits various blood component types by centrifugation. The bloodprocessing vessel 352 is interfitted within or otherwise attached to thechannel housing 204. Blood thus flows from the donor/patient 4, throughthe extracorporeal tubing circuit 10, and into the rotating bloodprocessing vessel 352. The blood within the blood processing vessel 352is separated into various blood component types and at least one ofthese blood component types (e.g., platelets, plasma, red blood cells)is preferably continually removed from the blood processing vessel 352for collection. Separated blood components, which are not beingcollected (e.g., red blood cells, white blood cells, and/or plasma) arealso removed from the blood processing vessel 352 and returned to thedonor/patient 4 via the extracorporeal tubing circuit 10.

Operation of the blood component separation device 6 is preferablycontrolled by one or more processors included therein, and mayadvantageously comprise a plurality of embedded personal computers toaccommodate interface with ever-increasing PC user facilities (e.g., CDROM, modem, audio, networking and other capabilities). In order toassist the operator of the apheresis system 2 with various aspects ofits operation, the blood component separation device 6 preferablyincludes a graphical interface 660.

Disposable Set: Extracorporeal Tubing Circuit

As illustrated in FIGS. 2A, 2B and 2C, two preferred preconnectedextracorporeal tubing circuits 10 and 10A are shown which are usable inaccordance with the present invention. In the alternative shown in FIGS.2A and 2B, tubing circuit 10 comprises a cassette assembly 110 and anumber of tubing assemblies 20, 50, 60, 80, 90, 100 and/or 950interconnected therewith. Generally, blood removal/return tubingassembly 20 provides a single needle interface between a donor/patient 4and cassette assembly 110, and blood inlet/blood component tubingsubassembly 60 provides the interface between cassette assembly 110 andblood processing vessel 352. Various combinations and/or permutations ofanticoagulant tubing assembly 50, platelet collection tubing assembly80, plasma collection tubing assembly 90, red blood cell collectionassembly 950 and vent bag tubing subassembly 100 may also beinterconnected with cassette assembly 110. As will be appreciated, theextracorporeal tubing circuit 10 and blood processing vessel 352 areinterconnected to combinatively present a closed, sterilizabledisposable set, preferably for a single use.

The blood removal/return tubing assembly 20 shown includes a singleneedle subassembly 30 interconnected with blood removal tubing 22, bloodreturn tubing 24 and anticoagulant tubing 26 via a common manifold 28.Among other options, blood removal tubing 22 may be provided with aY-connector 44 interconnected with a blood sampling subassembly 46.

The alternative embodiment shown in FIG. 2C is shown with like numbersrepresenting like elements with certain modifications represented withcertain lettered suffixes. For example, the tubing set 10A includes twodiscrete cassette assemblies 110A and 110B which incorporate some, butnot all of the features of the single cassette 110 of FIGS. 2A and 2B.Similarly, the access pressure module/sensor 134A/1200A and thereservoir 150A are discrete elements here and are not resident on or inthe cassette 110. This illustrates just one alternative embodimentusable herewith. Indeed, the present invention may be used with aplurality of single needle systems, like those shown here, see also forexample, U.S. Pat. No. 5,437,624, which is similar to the FIG. 2Calternative, or even double systems, though these are not shown here.

Nevertheless, a presently preferred cassette assembly 110 such as thatshown in FIGS. 2A and 2B will now be described in some detail. As such,cassette assembly 110 includes front and back molded plastic plates 112and 114 (see FIGS. 4A and 4B) that are hot-welded together to define arectangular cassette member 115 having integral fluid passageways. Thecassette assembly 110 further preferably includes a number of outwardlyextending tubing loops interconnecting various integral passageways. Theintegral passageways are also interconnected to the various tubingassemblies. Specifically, cassette assembly 110 preferably includes afirst integral anticoagulant passageway 120 a interconnected with theanticoagulant tubing 26 of the blood removal/return tubing assembly 20.The cassette assembly 110 further includes a second integralanticoagulant passageway 120 b and a pump-engaging, anticoagulant tubingloop 122 between the first and second integral anticoagulant passageways120 a, 120 b. The second integral anticoagulant passageway 120 b isinterconnected with anticoagulant tubing assembly 50. The anticoagulanttubing assembly 50 includes a spike drip chamber 52 connectable to ananticoagulant source (not shown), anticoagulant feed tubing 54 and asterilizing filter 56. During use, the anticoagulant tubing assembly 50supplies anticoagulant to the blood removed from a donor/patient 4 toreduce or prevent any clotting in the extracorporeal tubing circuit 10.

As shown, cassette assembly 110 also preferably includes a firstintegral blood inlet passageway 130 a interconnected with blood removaltubing 22 of the blood removal/return tubing assembly 20. The cassetteassembly 110 further includes a second integral blood inlet passageway130 b and a pump-engaging, blood inlet tubing loop 132 between the firstand second integral blood inlet passageways 130 a, 130 b. The firstintegral blood inlet passageway 130 a includes a first pressure-sensingmodule 134 and inlet filter 136, and the second integral blood inletpassageway 130 b includes a second pressure-sensing module 138. Thesecond integral blood inlet passageway 130 b is interconnected withblood inlet tubing 62 of the blood inlet/blood component tubing assembly60.

Blood inlet tubing 62 is also interconnected with input port 392 ofblood processing vessel 352 to provide whole blood thereto forprocessing, as will be described. To return separated blood componentsto cassette assembly 110, the blood inlet/blood component tubingassembly 60 further includes red blood cell (RBC)/plasma outlet tubing64, platelet outlet tubing 66 and plasma outlet tubing 68 interconnectedwith corresponding outlet ports 492 and 520, 456, and 420 of bloodprocessing vessel 352. The RBC/plasma outlet tubing 64 may include aY-connector 70 to interconnect tubing spurs 64 a and 64 b. The bloodinlet tubing 62, RBC/plasma outlet tubing 64, plasma outlet tubing 68and platelet outlet tubing 66 all preferably pass through first andsecond strain relief members 72 and 74 and a braided bearing member 76therebetween. This advantageously allows for a sealless interconnectionsuch as is taught in the U.S. patent to Ito, U.S. Pat. No. 4,425,112,inter alia. As shown, multi-lumen connectors 78 can be employed on thevarious tubing lines.

Platelet outlet tubing 66 also preferably includes a chamber 67positioned in close proximity to platelet collect port 420 of bloodprocessing vessel 352. During operation, a saturated bed of plateletswill form within chamber 67 and advantageously serve to retain whiteblood cells within chamber 67.

The cassette assembly 110 further preferably includes a pump-engaging,platelet tubing loop 142 interconnecting the first integral plateletpassageway 140 a and a second integral platelet passageway 140 b (seeFIG. 2B). The second integral platelet passageway 140 b includes firstand second spurs 144 a and 144 b, respectively. The first spur 144 a isinterconnected with platelet collection tubing assembly 80. The plateletcollection tubing assembly 80 can receive separated platelets duringoperation and includes platelet collector tubing 82 and plateletcollection bags 84 interconnected thereto via a Y-connector 86. Slideclamps 88 are provided on platelet collector tubing 82. The second spur144 b of the second integral platelet passageway 140 b is interconnectedwith platelet return tubing loop 146 of the cassette assembly 110 toreturn separated platelets to a donor/patient 4 (e.g., upon detection ofRBC spillover during platelet collection). For such purpose, plateletreturn tubing loop 146 is interconnected to the top of a blood returnreservoir 150 integrally formed by the molded front and back plates 112,114 of cassette member 115. One or more types of uncollected bloodcomponents, collectively referred to as return blood, will cyclicallyaccumulate in and be removed from reservoir 150 during use.

The plasma outlet tubing 68 of blood inlet/blood component tubingassembly 60 interconnects with a first integral plasma passageway 160 aof cassette assembly 110. Cassette assembly 110 further includes apump-engaging, plasma tubing loop 162 interconnecting the first integralplasma passageway 160 a and a second integral plasma passageway 160 b.The second integral plasma passageway 160 b includes first and secondspurs 164 a and 164 b. The first spur 164 a is interconnected to theplasma collection tubing assembly 90. The plasma collection tubingassembly 90 may be employed to collect plasma during use and includesplasma collector tubing 92 and plasma collection bag 94. A slide clamp96 is provided on plasma collector tubing 92. The second spur 164 b ofthe second integral plasma passageway 160 b is interconnected to aplasma return tubing loop 166 to return plasma to donor/patient 4. Forsuch purpose, the plasma return tubing loop 166 is interconnected to thetop of the blood return reservoir 150 of the cassette assembly 110.

The RBC/plasma outlet tubing 64 of the blood inlet/blood componenttubing assembly 60 is interconnected with integral RBC/plasma passageway170 of cassette assembly 110 (see FIG. 2B). The integral RBC/plasmapassageway 170 includes first and second spurs 170 a and 170 b,respectively. The first spur 170 a is interconnected with RBC/plasmareturn tubing loop 172 to return separated RBC/plasma to a donor/patient4. For such purpose, the RBC/plasma return tubing loop 172 isinterconnected to the top of blood return reservoir 150 of the cassetteassembly 110. The second spur 170 b may in one alternative embodiment beclosed off, or may be connected with an RBC/plasma collection tubingassembly 950 (see FIG. 2A) for collecting RBC/plasma during use. RBCcollection tubing assembly 950 preferably includes at least RBCcollector tubing 952, and RBC collection reservoir or bag 954. A sterilebarrier filter/drip spike assembly 956 may also be included and attachedto RBC bag 954.

A vent bag tubing assembly 100 may also preferably be interconnected tothe top of blood return reservoir 150 of cassette assembly 110. The ventbag tubing assembly 100 includes vent tubing 102 and a vent bag 104.During use, sterile air present since packaging within cassette assembly110, and particularly within blood return reservoir 150, may cyclicallypass into and back out of vent tubing 102 and vent bag 104. Additionalintegral passageways, integrated chambers and/or tubing loops could beincluded in cassette assembly 110 to perform the same or similarfunctions as the vent bag tubing assembly 100.

A first integral blood return passageway 190 a is preferablyinterconnected to the outlet 182 of blood return reservoir 150, and isfurther interconnected to a second integral blood return passageway 190b via a pump-engaging, blood return tubing loop 192. The second integralblood return passageway 190 b is interconnected with the blood returntubing 24 of the blood removal/return tubing assembly 20 to return bloodcomponents to the donor/patient 4 via needle assembly 30.

Tubing assemblies 20, 50, 60, 80, 90, 100 and 950 and cassette assembly110 are preferably made from PVC tubing and plastic components thatpermit visual observation and monitoring of blood/blood componentstherewithin during use. It should be noted that thin-walled PVC tubing(e.g., less than about 0.023 inch) may be employed for approved, steriledocking (i.e., the direct connection of two pieces of tubing) forplatelet collector tubing 82, plasma collector tubing 92 and RBC/plasmacollector tubings 952. In keeping with one preferred embodiment of theinvention, all tubing is preconnected before sterilization of thedisposable to assure that maximum sterility of the system is maintained.Alternatively, thicker-walled PVC tubing (e.g., about 0.037 inch ormore) may be employed for approved, sterile docking for these tubingsand is otherwise preferably utilized for pump-engaging tubing loops 132,142, 162 and 192.

Pump/Valve/Sensor Assembly

As noted, cassette assembly 110 may be mounted upon and operativelyinterface with the pump/valve/sensor assembly 1000 of blood componentseparation device 6 during use. The pump/valve/sensor assembly 1000 asillustrated in FIG. 3 preferably includes a cassette mounting plate1010, and a number of peristaltic pump assemblies, flow divert valveassemblies, pressure sensors and ultrasonic level sensors interconnectedto face plate 6 a of blood collection device 6 for pumping, controllingand monitoring the flow of blood and blood components throughextracorporeal tubing circuit 10 during use.

More particularly, anticoagulant pump assembly 1020 is provided toreceive anticoagulant tubing loop 122, blood inlet pump assembly 1030 isprovided to receive blood inlet tubing loop 132, platelet pump assembly1040 is provided to receive platelet tubing loop 142, plasma pumpassembly 1060 is provided to receive plasma tubing loop 162, and bloodreturn pump assembly 1090 is provided to receive blood return tubingloop 192. Each of these peristaltic pump assemblies includes arespective rotor and raceway between which the corresponding tubing loopis positioned to control the passage and flow rate of the correspondingfluid.

Platelet divert valve assembly 1100 is provided to receive plateletcollector tubing 82 and platelet return tubing loop 146, plasma divertvalve assembly 1110 is provided to receive plasma collector tubing 92and plasma return tubing loop 166, and RBC/plasma divert valve assembly1120 is provided to receive RBC/plasma return tubing loop 172 andRBC/plasma collector tubing 952. Platelet divert valve assembly 1100,plasma divert valve assembly 1110 and RBC/plasma divert valve assembly1120 each preferably include a rotary occluding member 1400 a, 1400 band 1400 c that is selectively positionable between respectivestationary occluding walls for diverting fluid flow through one tubingof the corresponding pairs of tubings.

Pressure sensors 1200 and 1260 (See also FIGS. 4A and 4B) are providedwithin pump/valve/sensor assembly 1000 to operatively engage the firstand second pressure-sensing modules 134 and 138 of cassette assembly 110through openings 1130 and 1140 of cassette mounting plate 1100.Similarly, ultrasonic level sensors 1300 and 1320 are provided tooperatively engage the blood return reservoir 150 of cassette assembly110 through openings 1160 and 1180 of cassette mounting plate 1010.

As shown in FIGS. 4A and 4B, presently preferred embodiments of firstand second pressure sensing modules 134, 138 of cassette assembly 110each comprise a circular diaphragm 134 a, 138 a positioned on a raisedcylindrical seat 134 b, 138 b formed into the back plate 114 of cassetteassembly 110 with a ring-shaped, plastic diaphragm retainer 134 c, 138 chot-welded to the raised cylindrical seats 134 b, 138 b to establish aseal therebetween. This arrangement allows the diaphragms 134 a, 138 ato be directly responsive to the fluid pressures within the first andsecond integral blood inlet passageways 130 a, 130 b, respectively, andpressure sensors 1200, 1260 to directly access the diaphragms 134 a, 138a through the ring-shaped retainers 134 c, 138 c. By monitoring thediaphragms 134 a, 138 a, the pressure sensors 1200, 1260 can monitor thefluid pressure within the first and second integral blood inletpassageways 130 a, 130 b. In this regard, it should also be noted thatsince first integral blood inlet passageway 130 a is in direct fluidcommunication with blood removal tubing 22, and since blood removaltubing 22 and blood return tubing 24 are fluidly interconnected via thecommon manifold 28, the first pressure sensing module 134 will beresponsive to and first pressure sensor 1200 will actually sense thesubstantially common pressure in both the blood removal tubing 22 andblood return tubing 24 during operation.

With further regard to the preferred first pressure sensing module 134and first pressure sensor 1200, FIG. 4A illustrates a preferred couplingarrangement that allows for the sensing of positive and negativepressure changes (i.e., causing outward and inward flexure of diaphragm134 a). More details of a preferred sensing apparatus of this type canbe found in the disclosure of U.S. Pat. No. 5,795,317 inter alia. Evenso, it may be noted here that a pressure sensing transducer 1224 engagesair channel member 1204 to sense positive and negative pressure changeswithin sensing module 134 and provide an output signal in responsethereto during use. As will be further described, the output signal ofpressure transducer 1224 can be employed to control the operation ofblood inlet pump 1030 and blood return pump 1090 during operation.

With regard to the preferred second pressure sensing module 138 andsecond pressure sensor 1260, FIG. 4B illustrates a direct contactcoupling approach that allows for sensing of positive pressure changes(i.e., causing outward flexure of diaphragm 138 a). Such contactcoupling facilitates loading since the precise position of the diaphragm138 a relative to the second pressure sensor 1260 is not critical. Asabove, more details of a preferred pressure sensor can be found in U.S.Pat. No. 5,795,317; inter alia. Pressure transducer 1264 provides anoutput signal responsive to positive pressure changes acting upondiaphragm 138 a.

Operation of Extracorporeal Tubing Circuit and Pump/Valve/SensorAssembly

In an initial priming mode of operation, blood return pump 1090 may beoperated in reverse to transfer a priming solution, which in a preferredembodiment may be whole blood, through blood removal/return tubingassembly 20, integral blood return passageway 190, blood return tubingloop 192 and into reservoir 150. Contemporaneously and/or prior to thereverse operation of blood return pump 1090, anticoagulant peristalticpump 1020 may be operated to prime and otherwise provide anticoagulantfrom anticoagulant tubing assembly 50, through anticoagulant integralpassageway 120, and into blood removal tubing 22 and blood return tubing24 via manifold 28. When lower level ultrasonic sensor 1320 senses thepresence of the priming solution or whole blood in reservoir 150 asignal is provided and blood component separation device 6 stops bloodreturn peristaltic pump 1090. During the priming mode blood inlet pump1030 is also operated to transfer priming solution or blood into bloodinlet integral passageway 130, through blood inlet tubing loop 132 andinto blood inlet/blood component tubing assembly 60 to prime the bloodprocessing vessel 352.

Then, in the preferred embodiment blood processing mode, the blood inletperistaltic pump 1030, platelet peristaltic pump 1040 and plasmaperistaltic pump 1060 are operated continuously, and the occludingmembers 1400 a, 1400 b, 1400 c are positioned for collection or returnof corresponding blood components, as desired. In the preferred singleneedle system, during a blood removal submode, blood return peristalticpump 1090 is not operated so that whole blood will pass into bloodremoval/return tubing assembly 20 and be transferred to processingvessel 352 via the cassette assembly 110 and blood inlet/blood componenttubing assembly 60. In the blood removal submode, all separated bloodcomponents are transferred from the processing vessel 352 to cassetteassembly 110, and uncollected components are passed into and accumulatein reservoir 150 up to a predetermined level at which upper levelultrasonic sensor 1300 provides signals used by blood componentseparation device 6 to end the blood removal submode and initiate ablood return submode. More particularly, the blood return submode isinitiated by forward operation of blood return peristaltic pump 1090. Inthis regard, it should be appreciated that in the blood return submodethe volume transfer rate of return blood through blood return tubingloop 192 utilizing blood return peristaltic pump 1090 is established byblood component separation device 6, according to a predeterminedprotocol, to be greater than the volume transfer rate through bloodinlet tubing loop 132 utilizing blood inlet peristaltic pump 1030. Assuch, the accumulated blood in reservoir 150 is transferred into theblood return tubing of blood removal/return tubing assembly 20 and backinto the donor/patient 4. When the accumulated return blood in reservoir150 is removed down to a predetermined level, lower level ultrasonicsensor 1320 will fail to provide signals to blood component separationdevice 6, whereupon blood component separation device 6 willautomatically stop blood return peristaltic pump 1090 to end the bloodreturn submode. This automatically serves to reinitiate the bloodremoval submode since in the preferred embodiments the blood inletperistaltic pump 1030 continuously operates.

During the blood processing mode, pressure sensor 1200 sensesnegative/positive pressure changes within the blood removal tubing 22and blood return tubing 26 via first integral blood inlet passageway 130a. Such monitored pressure changes are communicated to blood componentseparation device 6 which in turn controls blood inlet pump 1030 andreturn pump 1090 so as to maintain fluid pressures within predeterminedranges during the blood removal and the blood return submodes.Specifically, in one embodiment, during the blood removal submode, if anegative pressure is sensed that exceeds (i.e., is less than) apredetermined negative limit value, then blood component separationdevice 6 will slow down operation of blood inlet pump 1030 until thesensed negative pressure is back within an acceptable range. During theblood return submode, if a positive pressure is sensed that exceeds(i.e., is greater than) a predetermined positive limit value, then bloodcomponent separation device 6 will slow down operation of blood returnpump 1090 until the sensed positive pressure is back within anacceptable range.

In another embodiment, separation device 6 will pause all pumps when thepressure reaches an alarm point. In the draw cycle, device 6 can thenhold this pause until the pressure rises above the negative alarm pointor another discrete set point (such as −50 mmHg, for example). Anaudible squeeze beep sound or other warning alarm signal, message or thelike can be emitted by device 6 during this pump pause at least so longas the pressure remains below the alarm or other set point. Device 6 canfurther set or have a set time limit (for a period of for example 6seconds) for an automatic resolution during this pause after which, ifthere is no resolution, a regular/full alarm condition occurs.Resolution is the pressure rise to above the alarm or other pre-selectedset point. The regular/full alarm condition involves complete stoppageof all pumps and requires operator intervention to re-start the pumps.The advantage in this embodiment is to minimize operator interventionwith pressure alarms which may automatically resolve or may be resolvedwith mere donor/patient intervention by the donor/patient squeezing hisor her fist in response to the squeeze beep warning signal. This fistsqueezing could raise the pressure in the donor/patient's accessvasculature and/or could otherwise properly expand a collapsed vein toestablish proper seating of the access/draw needle therein.

Note, as mentioned above, certain access/draw pressure conditionssignify no flow or improper flow characteristics, which may need to beaddressed by an operator. However, some of these pressure conditions maybe resolved prior to operator intervention by the donor/patient (fistsqueezing, e.g.), or by the machine (a pump pause or slowing may allowthe pressure in the donor/patient's vasculature to raise). Thus, in theknown example where the access/draw needle may become improperly seatedor blocked within the donor/patient access site, the access/drawpressures sensed by the extracorporeal processing system can beinterpreted as indicating the problem and then activating an alarm of awarning nature for donor/patient intervention as well as initiating pumpand/or other fluid flow controls such as slowing or stopping the flow orflows or pump or pumps. If either of these initial procedures fails toresolve the situation (or if an ultimate alarm point is reached), thenthe processing system may signal a distinct alarm for operatorintervention.

In another embodiment, which may be used with either alternativedescribed above, device 6 may be configured to interpret a particularquantity of warning alarms occurring within a particular time period asa trigger for setting a regular/full alarm. Thus, whether device 6merely slows the pumps or pauses them for a period of time as a warningalarm in response to a low pressure signal, if the warning alarm occurstoo many times during a particular time period, then device 6 goes toregular/full alarm and stops the pumps and alerts the operator tointervene and check certain elements of the system. In combination withthe second alternative described above (where the pumps pause for aparticular time period), this alternative provides for a full alarmcondition even if the pressure resolves (i.e., rises above the alarm orother set point) each time within the designated period. An example of aquantity per period under this alternative is three warnings occurringin three minutes. The advantage is that even if resolution appears to beautomatically or with donor/patient assistance readily gained, somethingmore serious may still be wrong at least insofar as the operator shouldintervene to ensure proper needle placement in the vein or to checkwhether the pressure cuff (if used, see FIG. 10, e.g.) is properlyinflated or to make adjustments to the donor flow rate.

A third alternative embodiment, which may be used alone or in anycombination with the above embodiments, involves a single needleadaptation. As described hereinabove, and as understood in the art, insingle needle systems generally, separated blood components destined forreturn to the donor/patient are first accumulated in a reservoir, suchas reservoir 150 of the cassette 110 described above. Thus, during bloodprocessing operation, blood is cyclically accumulated in the reservoirand then cyclically pumped back to the donor/patient. In a pressurealarm situation, the accumulated blood components in the reservoir maybe pumped back to the donor/patient strategically in response to thealarm as follows. If the pressure drops to the warning point (or withina certain pre-selected point of the warning or full alarm point) and thedraw cycle (or reservoir 150 accumulation cycle) is greater than apre-selected percentage of completion (e.g., 90%), then the warningalarm condition may include a switch to the blood return mode byswitching on the blood return pump (such as pump 1090, hereinabove) andpausing (or slowing) all of the other pumps according to theabove-described alternative embodiments. This embodiment may either beused alone or with any one or more of the other alternatives describedherein, such as for example counting against the set quantity per periodalternative (the three times in three minutes example, above). Otheroptions may also be configured herewith, as for example, disabling thisswitch to return in certain phases of a blood processing procedure (forexample, not allowing a switch to return during the first five drawcycles or any other time as may be appropriate).

In yet another alternative embodiment particularly involving a fluidchamber such as chamber 67 (see FIGS. 1 and 2A) preferred embodiments ofwhich being described in various U.S. and corresponding foreign patents,such as U.S. Pat. Nos. 5,674,173; 5,722,926; 5,906,570; 5,913,768;5,939,319 and 5,951,877; inter alia, a resolvable low access pressuresituation will preferably not be permitted to interrupt the flow ofcomponents and fluids thereinto and therethrough. Thus, a warning alarmcondition as generally described above may be made to stop or pause allpumps (according to the selected alternative above) except for theplatelet pump (such as pump 1040 hereinabove) which may be made tocontinue to run for a pre-selected period (for example, two seconds)during which time the low access pressure condition will either resolve(i.e., rise above the alarm or other set point) or the regular/fullalarm will then occur and device 6 will stop all pumps for operatorintervention.

In the above-described alternative embodiments, generally only one alarmpressure point is involved. This is distinctive from many prior,conventional systems which incorporate a warning alarm point as anadjunct to an ultimate low pressure alarm point at which theregular/full alarm condition is met. In these prior, conventionalsystems the warning alarm point is some set level higher than theultimate low pressure point such that as the access/draw pressure fallsfrom the desirable operation level, it first reaches the warning alarmpoint and the processing device can then signal with a squeeze beep orother message to the operator and/or the donor/patient to try to raisethe access pressure as by squeezing of the donor/patient fist. Then, inthese prior, conventional systems either the access pressure is raised(or at least stopped from falling) during which time the bloodprocessing machine continues to operate (even if at reduced rates), orthe access pressure continues to fall until it reaches the ultimate lowlevel point whereupon the processing device signals the regular/fullalarm condition and stops all flows.

In contrast, the above alternatives do not require a bottom or ultimatelow pressure level point for activation of the regular/full alarm.Rather, the regular/full alarm will instead be signaled by the reachingthe end of the resolution pause period or the pre-selected quantity ofwarnings per period (and/or the limits of the other options as describedherein).

Even so, the above-described alternatives of the present invention mayalso be incorporated with an ultimate low level pressure point as well.Thus, when there is a failure to resolve in either the pause period orthe quantity per period has been reached, device 6 may instead of goingto a regular/full alarm condition including full pump stoppage mayinstead run the pumps at an adjusted percentage of full operationalspeeds (or could stop some pumps and/or maintain others such as theplatelet pump as above). This would prevail until resolution or operatorintervention (an intermediate alarm condition could be signaled here) oruntil the ultimate low pressure level is reached at which point thepumps are all stopped and the regular/full alarm condition is signaled.Note, an adjusted percentage of full speed option here is preferablyusable on/with systems which use a warning alarm point in addition to anultimate low alarm point; thus, the adjusted percentage option describedhere would preferably only become effective in the pressure intervalafter the warning point is reached with the pause period expired, butonly before the ultimate low alarm point is reached. Often, the adjustedpercentage will not be preferable because the warning alarm point willbe set at a low flow/low pressure level such that the pump(s) willpreferably remain paused until resolution, or if there is no resolution,then merely stopped. Re-starting such pumps without resolution wouldlikely only exacerbate the situation/problem.

A few variations of what the warning alarm limits, which would triggerthe selected alternative alarm occurrences described above are alsocontemplated by the present invention. For example, the access or drawpressure alarm limit in prior, conventional systems was usually set ator around an ultimate low pressure limit of −350 mmHg. This limit mayhave had an empirical basis. Warning limits may have been set therealso, or at some incremental higher level. Nevertheless, a presentlypreferred alarm limit may be adjusted or adjustable in view of certainpre-selected parameters. In particular and in the case where there is asingle needle having a single pressure sensor (such as sensor 1200 in apreferred embodiment as described above) applied to sense both theinlet/draw pressure as well as the return pressure, certainrelationships can be used to adjust both the draw and the return limits.Thus, an access/draw alarm pressure limit may be defined by theequation:Draw Alarm Limit=Config+75−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H_(n))

-   -   where,        -   Config=a configuration pre-selected pressure (e.g., −250            mmHg.)        -   Q_(in)=flow rate in the inlet tubing line;        -   H_(in)=Hematocrit in the inlet tubing line;        -   Q_(n)=flow rate in the needle; and        -   H_(n)=Hematocrit in the needle.

The above equation is in part theoretically derived depending upongeometry (i.e. the lengths and diameters of the inlet tubing and needle.As such, this equation resembles a pipe flow equation. It is alsodependent on the viscosity of the blood flowing there through. Theequation takes the pressure drop due to the needle, the inlet line andhematocrit into account. The above equation is presently preferred forplatelet collection tubing sets.

A similar presently preferred equation for RBC/plasma collection tubingsets is as follows:Draw Alarm Limit=Config+75−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H_(n))where the variables are defined as above. The coefficients here presumean 18 gauge (ga) needle is used. In both of the above equations, amaximum negative limit of −350 mmHg is preferably imposed, partly indeference to historical empirical development.

Similar maximum return pressure alarm limits may be calculated by device6 such that for platelet tubing sets:Return Alarm Limit=Config−50−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H_(n));and for RBC/plasma tubing sets:Return Alarm Limit=Config−50−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H_(n));where the above definitions and assumptions remain except the configlimit which would preferably be changed to a value such as +310 mmHg,and the maximum positive limit being set at +400 mmHg as an override ofthe equation (s). Further, Q_(n) is negative in the return equations,and the hematocrit being returned is determined by monitoring thehematocrit in the reservoir 150 in the previous draw cycle. Theseequations also take into account whether there may be recirculation inthe draw line as pulling from the return line.

In an embodiment of this invention preferably using a single-needleblood draw, three alarm levels may be triggered. The first-level alarmallows a short pause period in which minor glitches such as lack ofdonor attention to squeezing a ball to enhance blood flow can becorrected. Preferably the first-level alarm does not pause the plateletpump, which controls fluid flow through the leukocyte reduction chamber.The second-level alarm, which is used during plasma and plateletcollection, but is not needed during RBC collection, allows a slow-downperiod so that the leukocyte reduction system (LRS) can keep operatingwhile an operator resolves the problem, e.g., correcting needlepositioning. The third-level alarm shuts down operation of theblood-collection pumps to allow the operator to deal with majorproblems, which prevent flow entirely.

The first-level alarm pauses all pumps (except the platelet pump whichmaintains flow through the leukocyte reduction system (LRS) chamber) fora specified period of time, preferably about 1-5 seconds, and morepreferably about 3 seconds, and provides a signal, such as a visible oraudible signal, to alert the operator. The signal may persist or berepeated until the sensed pressure returns to a value within thespecified range, or the signal may be of short duration.

The second-level alarm causes the inlet pump flow and anticoagulant pumpflow to be reduced, e.g., by a specified flow-reduction factor, whilemaintaining flow through the LRS chamber, stopping the plasma pump, andsignaling the operator. The reduced-flow condition is maintained untilthe operator intervenes to clear the problem, e.g., by readjusting theneedle, waking the donor up, adjusting the pressure cuff, or takingother appropriate action. The specified flow-reduction factor ispreferably about 0.5 (flow rate is reduced by half). It should be lowenough to keep from triggering another first-level alarm, but highenough so that flow through the LRS chamber is maintained. Asecond-level alarm also provides a continuous audible and/or visualsignal to the operator.

The third-level alarm causes all pumps to stop and provides a signal tothe operator.

A first-level alarm is triggered when the inlet pressure measured by thesensor is below a specified sensor pressure. This specified sensorpressure is calculated as a function of the specified system pressurewhich would trigger a first-level alarm, and the following parameters:instantaneous inlet pump flow during the draw phase, inlet pumphematocrit, anticoagulant (AC) ratio during platelet and plasmacollection, donor hematocrit, a configuration specified system pressure,the flow rate in the inlet tubing line, the hematocrit in the inlettubing line, the flow rate in the needle and the hematocrit in theneedle. A calculation is necessary because the pressure readout from thesensor, which is preferably located just upstream from the inlet pump,may not be the same as the actual pressure in the system. The lowerthreshold of the specified sensor pressure is calculated in accordancewith the following formula useful for the Gambro Trima® V 4 and V 5products using a 17 ga needle:specified sensor pressure=Config+75−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n));where Config is a configuration specified system pressure (mmHg.),Q_(in) is the flow rate in the inlet tubing line (ml/min.); H_(in) isthe Hematocrit in the inlet tubing line; Q_(n) is the flow rate in theneedle (ml/min.); and H_(n) is the Hematocrit in the needle.

The configuration specified system pressure should not be so high as totrigger false alarms, nor so low as to fall outside the capability ofthe sensor. Preferably, the configuration specified system pressure isbetween about −100 to about −250 mmHg, and more preferably about −250mmHg.

If the sensed pressure which triggered the first-level alarm returns toa value above both the specified sensor pressure and a specifiedalarm-disabling sensor pressure within a specified delay time e.g.,about 1 to about 10 seconds, preferably about 2 to about 6 seconds, andmore preferably, about 5 seconds (i.e., the first-level alarm conditionresolves), the first-level alarm is disabled, pumping is resumed and ifthe signal has been continuous, it terminates. The specifiedalarm-disabling system pressure is preferably from about 0 to about −150mmHg, and more preferably about −50 mmHg. The specified sensor pressurerequired to disable a first-level alarm is calculated according to theabove formula used for calculating the specified sensor pressurerequired to trigger a first-level alarm.

If a specified number, e.g. about three, first-level alarms occur andare resolved within a specified period, e.g., about 1 to about 10minutes, preferably about 5 minutes, and preferably also if plasma andplatelet collection are not yet complete, a second-level alarm istriggered. If plasma and platelet collection are finished at this point,a third level alarm is triggered.

If the sensed pressure that triggered the first-level alarm does notreturn to a value above the specified alarm-disabling sensor pressurewithin the specified delay time, then a third-level alarm is triggered.

During the slow-down period, which occurs in response to thesecond-level alarm trigger, the operator may resolve the problem andreturn the flow rate to full volume, or may select a reduced flow rateor shut down the system. The second-level alarm condition persists untilresolved by the operator or until a third-level alarm is triggered.

FIG. 11 is a flow diagram depicting a preferred embodiment of theinvention utilizing three alarm levels. If the inlet pressure sensed, P,is less than the specified pressure, P_(S), then a first-level alarm istriggered. After the specified delay time, if the pressure has not risento a selected pressure, which causes disabling of the first alarmcondition, P_(D), then a third-level alarm is triggered. The operatormay then intervene and shut down all pumps, may resolve the problem andreturn the system to normal flow conditions, or may slow down the flowrate. If the pressure has risen to greater than or equal to P_(D) by theend of the specified delay time, and if the first-level alarm conditionwas the third one triggered within a specified period (preferably 5minutes), and if plasma and platelet collections are ongoing, then asecond-level alarm condition is created. If first-level alarm conditionwas not the third one triggered within the specified period, the systemreturns to normal operation. If plasma and platelet collections havebeen completed, a third-level alarm system with shut down of the pumpsis triggered. During the slow-down period created by the second-levelalarm condition, operator intervention is required to resolve theproblem and return the system to full operation, shut it down or slowthe flow rate. But if, during the slow-down period of the second-levelalarm condition, the pressure drops below P_(S), triggering a furtherfirst-level alarm condition in which the pumps are paused, a third-levelalarm condition is triggered.

A third-level alarm condition is terminated when the operator intervenesto terminate the session, by shutting down the system, or if theoperator is able to solve the problem, the third-level alarm conditionis terminated by the operator returning the system to normal flow. Ifthe operator determines that the process can continue at a lower flowrate without triggering repeated alarms, the operator may slow down theflow rate. In a single-needle apheresis system, shutting down the systemmay include returning blood in the system to the donor before shuttingdown the system entirely.

In a preferred embodiment, a return pressure alarm is provided. Too higha return pressure may indicate that blood is being sent somewhere elsethan the patient's vein, a condition that requires operator interventionto resolve. When the return pressure sensor senses a reading greaterthan a specified reading, a return pressure alarm is provided whichstops the return pump as well as all other pumps and provides a signalto the operator. The sensor reading may be different from the actualpressure in the line, therefore, for the Gambro Trima® V 4 and V5products using a 17 ga needle, the specified reading is calculated bythe formula:specified sensor pressure=Config−50−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n));where Config is the configuration specified system pressure (mmHg),Q_(in) is the flow rate in the inlet tubing line (ml/min.); H_(in) isthe Hematocrit in the inlet tubing line; Q_(n) is the flow rate in theneedle (ml/min.); and H_(n) is the Hematocrit in the needle.

FIG. 12 is a block diagram showing components of a fluid separationcontrol system for triggering three alarm levels. A pressure monitorconnected to the fluid separation system, preferably monitoring pressureat an inlet pump of said system, is connected to a processor. Based onsystem parameters and specified system alarm trigger pressures, theprocessor calculates the sensor pressure that should trigger the alarms.The processor sends a signal to flow control devices that stop, startand slow selected system pumps.

Returning now to the general description of the blood processingoperation, the second pressure sensor 1260 monitors the positivepressure within the second integral blood inlet passageway 130 b andblood inlet tubing 62 after the inlet pump 1030. If such sensed positivepressure exceeds a predetermined maximum value, blood componentseparation device 6 will initiate appropriate responsive action,including, for example, slowing or stoppage of the centrifuge andperistaltic pumps.

During the blood processing mode, blood component separation device 6controls the operation of anticoagulant pump 1020 according to apredetermined protocol and responsive to signals provided by AC sensor1700 (e.g., FIG. 3) which may indicate a depleted anticoagulant source.Also, blood component separation device 6 also controls the operation ofdivert assemblies 1100, 1110, 1120 according to predeterminedinstructions and further pursuant to any detect signals provided by anRBC spillover detector 1600 (FIG. 3). In the latter regard, if an RBCspillover in the separated platelet stream is detected, blood componentseparation device 6 will automatically cause occluder member 1400 a todivert the separated platelet stream to the return reservoir 150 untilthe RBC spillover has cleared, thereby keeping red blood cells fromundesirably passing into platelet collector tubing assembly 80.

In normal operation, whole blood will pass through needle assembly 30,blood removal tubing 22, cassette assembly 110 and blood inlet tubing 62to processing vessel 352. The whole blood will then be separated invessel 352. A platelet stream will pass out of port 420 of the vessel,through platelet tubing 66, back through cassette assembly 110, and willthen be either collected in collector assembly 80 or diverted toreservoir 150. Similarly, separated plasma will exit vessel 352 throughport 456 to plasma tubing 68 back through cassette assembly 110, andwill then either be collected in plasma tubing assembly 90 or divertedto reservoir 150. Further, red blood cells and plasma (and potentiallywhite blood cells) may pass through ports 492 and 520 of vessel 352through RBC/plasma tubing 64, through cassette assembly 110 and intoreservoir 150. Alternatively, during an RBC collection proceduredescribed generally hereinbelow, separated RBCs will be delivered toRBC/plasma collector tubing assembly 950 through tubing 952 forcollection.

As noted above, when uncollected platelets, plasma, and RBC/plasma (andpotentially white blood cells) have accumulated in reservoir 150 up toupper ultrasonic level sensor 1300, operation of return peristaltic pump1090 will be initiated to remove the noted components from reservoir 150and transfer the same back to the donor/patient 4 via the return tubing24 and needle assembly 20. When the fluid level in the reservoir 150drops down to the level of the lower ultrasonic level sensor 1320, thereturn peristaltic pump 1090 will automatically turn off reinitiatingthe blood removal submode. The cycle between blood removal and bloodreturn submodes will then continue until a predetermined amount ofplatelets or other collected blood components have been harvested.

In one embodiment, reservoir 150 and upper and lower ultrasonic sensors1300 and 1320 are provided so that, during the blood processing mode,approximately 50 milliliters of return blood will be removed fromreservoir 150 during each blood return submode and accumulated duringeach blood removal submode. In such an embodiment, lower and upper leveltriggering by ultrasonic sensors 1300 and 1320 occurs at fluid volumesof about 15 milliliters and 65 milliliters, respectively, withinreservoir 150. For such embodiment, it is also believed desirable toprovide for a volume transfer operating rate range of about 30 to 300milliliters/minute through blood return tubing loop 192 utilizing returnpump 1090, and a volume transfer operating rate range of about 20 to 140milliliters/minute through blood inlet tubing loop 132 utilizing inletpump 1030. Additionally, for such embodiment the maximum pressure limitsmay be altered slightly such that a negative pressure limit of about−250 mmHg and positive pressure limit of about 350 mmHg may beappropriate for controlling the speed of inlet pump 1030 and return pump1090, respectively, in response to the pressures sensed in firstpressure sensing module 134. A positive pressure limit of about 1350mmHg within second sensing module 138 is believed appropriate fortriggering slow-down or stoppage of the centrifuge and pumps.

Channel Housing

A preferred channel assembly 200 is illustrated in FIGS. 1, 5 and 6 andincludes a channel housing 204 which is disposed on the rotatablecentrifuge rotor assembly 568 (see FIG. 1) and which receives adisposable blood processing vessel 352. Referring more specifically toFIGS. 5-6, the channel housing 204 has a generally cylindrically-shapedperimeter 206 with a diameter of preferably no more than about 10 inchesto achieve a desired size for the blood component separation device 6(e.g., to enhance its portability). An opening 328 extendslongitudinally through the channel housing 204 and contains an axis 324(shown as a center dot in FIG. 6) about which the channel housing 204rotates. The channel housing 204 may be formed from materials such asdelrin, polycarbonate, or cast aluminum and may include various cut-outsor additions to achieve weight reductions and/or rotational balance.

The primary function of the channel housing 204 is to provide a mountingfor the blood processing vessel 352 such that the blood may be separatedinto the blood component types in a desired manner. In this regard, thechannel housing 204 includes a generally concave channel 208 in whichthe blood processing vessel 352 is positioned. The channel 208 isprincipally defined by an inner channel wall 212, an outer channel wall216 which is radially spaced from the inner channel wall 212, and achannel base 220 which is positioned therebetween. The channel 208 alsoextends from a first end 284 generally curvilinearly about a rotationalaxis 324 of the channel housing 204 to a second end 288 such that acontinuous flow path may be provided about the rotational axis 324.

The blood processing channel vessel 352 is removably disposed within thechannel 208. Generally, the channel 208 desirably allows blood to beprovided to the blood processing vessel 352 during rotation of thechannel housing 204, to be separated into its various blood componenttypes by centrifugation, and to have various blood component typesremoved from the blood processing vessel 352 during rotation of thechannel housing 204. For instance, the channel 208 is configured toallow for the use of high packing factors (e.g., generally a valuereflective of how “tightly packed” the red blood cells and other bloodcomponent types are during centrifugation). Moreover, the channel 208also desirably interacts with the blood processing vessel 352 duringcentrifugation (e.g., by maintaining a desired contour of the bloodprocessing vessel 352).

The above-identified attributes of the channel 208 are providedprimarily by its configuration. In this regard, the channel housing 204includes a blood inlet slot 224 which is generally concave and whichintersects the channel 208 at its inner channel wall 212 insubstantially perpendicular fashion. A blood inlet port assembly 388 ofthe disposable set 10 which leads to the interior of the bloodprocessing vessel 352 is disposed in this blood inlet slot 224 such thatblood from the donor/patient 4 may be provided to the blood processingvessel 352 when in the channel 208.

As illustrated in FIGS. 5-6, an RBC dam 232 of the channel 208 isdisposed in a clockwise direction from the blood inlet slot 224 andwhose function is to preclude RBCs and other large cells such as WBCsfrom flowing in a clockwise direction beyond the RBC dam 232. Generally,the surface of the RBC dam 232 which interfaces with the fluidcontaining volume of the blood processing vessel 352 may be defined as asubstantially planar surface or as an edge adjacent the collect well236. At least in that portion of the channel 208 between the blood inletport 224 and the RBC dam 232, blood is separated into a plurality oflayers of blood component types including, from the radially outermostlayer to the radially innermost layer, red blood cells (“RBCs”), whiteblood cells (“WBCs”), platelets, and plasma. The majority of theseparated RBCs are removed from the channel 208 through an RBC outletport assembly 516 which is disposed in an RBC outlet slot 272 associatedwith the channel 208, although at least some RBCs may be removed fromthe channel 208 through a control port assembly 488 which is disposed ina control port slot 264 associated with the channel 208.

The RBC outlet port slot 272 is disposed in a counterclockwise directionfrom the blood inlet slot 224, is generally concave, and intersects thechannel 208 at its inner channel wall 212 in substantially perpendicularfashion. An RBC outlet port assembly 516 to the interior of the bloodprocessing vessel 352 is disposed in this RBC outlet slot 272 such thatseparated RBCs from the apheresis procedure may be continually removedfrom the blood processing vessel 352 when in the channel 208 (e.g.,during rotation of the channel housing 204).

The control port slot 264 is disposed in a counterclockwise directionfrom the RBC outlet slot 272, is generally concave, and intersects thechannel 208 at its inner channel wall 212 in substantially perpendicularfashion. A control port assembly 488 to the interior of the bloodprocessing vessel 352 is disposed in the control port slot 264.

The portion of the channel 208 extending between the control port slot264 and the RBC dam 232 may be characterized as the first stage 312 ofthe channel 208. The first stage 312 is configured to remove primarilyRBCs from the channel 208 by utilizing a reverse flow in relation to theflow of platelet-rich plasma in the channel 208, which is in a clockwisedirection. In this regard, the outer channel wall 216 extends along acurvilinear path from the RBC dam 232 to the blood inlet slot 224generally progressing outwardly away from the rotational axis 324 of thechannel housing 204. That is, the radial disposition of the outerchannel wall 216 at the RBC dam 232 is less than the radial dispositionof the outer channel wall 216 at the blood inlet slot 224. The portionof the RBC outlet slot 272 interfacing with the channel 208 is alsodisposed more radially outwardly than the portion of the blood inletslot 224 which interfaces with the channel 208.

In the first stage 312, blood is separated into a plurality of layers ofblood component types including, from the radially outermost layer tothe radially innermost layer, red blood cells (“RBCs”), white bloodcells (“WBCs”), platelets, and plasma. As such, the RBCs sedimentagainst the outer channel wall 216 in the first stage 312. Byconfiguring the RBC dam 232 such that it is a section of the channel 210which extends further inwardly toward the rotational axis 324 of thechannel housing 204, this allows the RBC dam 232 to retain separatedRBCs and other large cells as noted within the first stage 312. That is,the RBC dam 232 functions to preclude RBCs from flowing in a clockwisedirection beyond the RBC dam 232.

Separated RBCs and other large cells are removed from the first stage312 utilizing the above-noted configuration of the outer channel wall216 which induces the RBCs and other large cells to flow in acounterclockwise direction (e.g., generally opposite to the flow ofblood through the first stage 312). Specifically, separated RBCs andother large cells flow through the first stage 312 along the outerchannel wall 216, past the blood inlet slot 224, and to an RBC outletslot 272. In order to reduce the potential for counterclockwise flowsother than separated RBCs being provided to the control port assembly488 disposed in the control port slot 264 such that there is a sharpdemarcation or interface between RBCs and plasma proximate the controlport slot 264, a control port dam 280 of the channel 208 is disposedbetween the blood inlet slot 224 and the RBC outlet slot 272. That is,preferably neither WBCs nor any portion of a buffy coat, disposedradially adjacent to the separated RBCs, is allowed to flow beyond thecontrol port dam 280 and to the control port slot 264. The “buffy coat”includes primarily WBCs, lymphocytes, and the radially outwardmostportion of the platelet layer. As such, substantially only the separatedRBCs and plasma are removed from the channel 208 via the RBC controlslot 264 to maintain interface control as noted.

The flow of RBCs to the control port assembly 488 is typicallyrelatively small. Nonetheless, the ability for this flow is highlydesired in that the control port assembly 488 functions in combinationwith the RBC outlet port assembly 516 to automatically control theradial position of an interface between separated RBCs and the “buffycoat” in relation to the RBC dam 232 by controlling the radial positionof an interface between separated RBCs and plasma in relation to thecontrol port assembly 488. The control port assembly 488 and RBC outletport assembly 516 automatically function to maintain the location of theinterface between the separated RBCs and the buffy coat at a desiredradial location within the channel 208 which is typically adjacent theRBC dam 232 such that there is no spillover of RBCs beyond the RBC dam232. This function is provided by removing separated RBCs from thechannel 208 at a rate which reduces the potential for RBCs and the otherlarge cells as noted flowing beyond the RBC dam 232 and contaminatingthe platelet collection.

Separated platelets, which are disposed radially inwardly of the RBClayer and more specifically radially inwardly of the buffy coat, flowbeyond the RBC dam 232 with the plasma (e.g., via platelet-rich plasma)in a clockwise direction. A generally funnel-shaped platelet collectwell 236 is disposed in a clockwise direction from the RBC dam 232 andis used to remove platelets from the channel 208 in the platelet-richplasma. The configuration of the platelet collect well 236 is defined byonly part of the outer channel wall 216. The remainder of the plateletcollect well 236 is defined by the blood processing vessel 352 whenloaded in the channel 208.

The outer channel wall 216 is further configured to receive the plateletcollect tube 424. Platelet collect tube recess 254 is disposed yetfurther radially outwardly from the platelet support recess 249 toprovide this function. As such, the platelet collect tube 424 may extendradially outwardly from the outer sidewall 376 of the blood processingvessel 352, extend upwardly through the platelet collect tube recess 254behind or radially outwardly from the support 428, and extend above thechannel housing 204.

Platelet-poor plasma continues to flow in a clockwise direction throughthe channel 208 after the platelet collect well 236 and may be removedfrom the channel 208. In this regard, the channel 208 further includes agenerally concave plasma outlet slot 256 which is disposed proximate thesecond end 288 of the channel 208 and intersects the channel 208 at itsinner channel wall 212 in substantially perpendicular fashion. A plasmaoutlet port assembly 452 to the interior of the blood processing vessel352 is disposed in this plasma outlet slot 256 such that plasma may becontinually removed from the blood processing vessel 352 during anapheresis procedure (e.g., during continued rotation of the channelhousing 204). This plasma may be collected and/or returned to thedonor/patient 4. In order to increase the number of platelets that areseparated and removed from the vessel 352 in a given apheresisprocedure, the configuration of the channel 208 between the plateletcollect well 236 and the plasma outlet slot 256 may be such thatplatelets which separate from plasma in this portion of the channel 208actually flow in a counterclockwise direction back towards the plateletcollect well 236 for removal from the channel 208. This may be providedbe configuring the outer channel wall 216 such that it extends generallycurvilinearly about the rotational axis 324 from the platelet collectwell 236 to the plasma outlet slot 256 progressing generally inwardlytoward the rotational axis 324 of the channel housing 204. Consequently,the portion of the channel 208 including the platelet collect well 236and extending from the platelet collect well 236 to the second end 288may be referred to as a second stage 316 of the channel 208.

The channel 208 is also configured to provide platelet-poor plasma tothe control port slot 264 and thus to the control port assembly 488 inorder to assist in automatically controlling the interface between theRBCs and the buffy coat in relation to the RBC dam 232. In this regard,the first end 284 of the channel 208 is interconnected with the secondend 288 of the channel 208 by a connector slot 260. With the first end356 and second end 364 of the blood processing vessel 352 being fluidlyjoined, the connection therebetween may be disposed in this connectorslot 260. As such, a continuous flowpath is provided within the bloodprocessing vessel 352 and, for purposes of the automatic interfacecontrol feature, RBCs may flow to the control port slot 264 in acounterclockwise direction and plasma may flow to the control port slot264 in a clockwise direction. The portion of the channel 208 extendingfrom the first end 284 to the control port slot 264 may be referred toas a third stage 320 of the channel 208.

The configuration of the channel 208 retains the blood processing vessel352 within the channel 208 throughout the apheresis procedure. This isparticularly relevant in that the channel housing 204 is preferablyrotated a relatively high rotational velocities, such as about 3,000RPM.

Disposable Set: Blood Processing Vessel

As described, the blood processing vessel 352 is removably disposedwithin the channel 208 for directly interfacing with and receiving aflow of blood in an apheresis procedure. The use of the blood processingvessel 352 alleviates the need for sterilization of the channel housing204 after each apheresis procedure and the vessel 352 may be discardedto provide a disposable system. Two preferable characteristics of theblood processing vessel 352 are that it is constructed such that it issufficiently rigid to be free standing in the channel 208. However, itis also preferably sufficiently flexible so as to substantially conformto the shape of the channel 208 during an apheresis procedure.

The blood processing vessel 352 includes an inner sidewall 372 and anouter sidewall 376. In the illustrated embodiment, the blood processingvessel 352 is formed by sealing two pieces of material together (e.g.,RF welding). More specifically, the inner sidewall 372 and outersidewall 376 are connected along the entire length of the bloodprocessing vessel 352 to define upper and lower seals. Seals are alsoprovided on the ends of the vessel 352. By utilizing two separate sheetsto form the blood processing vessel 352, a “flatter” profile may also beachieved. This type of profile is beneficial during rinseback, and alsofacilitates loading and unloading of the vessel 352 relative to thechannel 208.

Centrifuge Rotor Assembly

The channel assembly 200 is mounted on the centrifuge rotor assembly568, which rotates the channel assembly 200 to separate the blood intothe various blood component types by centrifugation. A preferredcentrifuge rotor assembly 568 is described in more detail in U.S. Pat.No. 5,722,946, inter alia.

Apheresis Protocol

One protocol that may be followed for performing an apheresis procedureon a donor/patient 4 utilizing the above-described system 2 will now besummarized. Initially, an operator loads the cassette assembly 110 ontothe pump/valve/sensor assembly 1000 of the blood component separationdevice 6 and hangs the various bags (e.g., bags 114, 94, 84) on theblood component separation device 6. The operator then loads the bloodprocessing vessel 352 into the channel 208 which is disposed on thechannel housing 204 which is in turn mounted on the centrifuge rotorassembly 568.

With the extracorporeal tubing circuit 10 and the blood processingvessel 352 loaded in the above-described manner, the circuit 10 andvessel 352 are pressure tested to verify that there are no leaks. Thedonor/patient 4 is then fluidly interconnected with the extracorporealtubing circuit 10 (by inserting an access needle 32 into thedonor/patient 4). Moreover, the anticoagulant tubing 54 is primedbetween the anticoagulant supply (which interfaces with the spike dripmember 52) and the manifold 28. Furthermore, blood return tubing 24 isprimed by running the blood return peristaltic pump 1090 pump in reverseto draw priming solution through the blood return tubing 24, and intothe reservoir 150 until solution is detected by the low level sensor1320. The blood processing vessel 352 must then also be primed for theapheresis procedure.

When the blood processing vessel 352 contains blood and/or bloodcomponents throughout its entirety, the rotational velocity of thechannel housing 204 is increased to its normal operation speed fromabout 2,750 RPM to about 3,250 RPM for a rotor diameter of about 10″,and preferably about 3,000 RPM.

During the apheresis procedure, blood component types are separated fromeach other and removed from the blood processing vessel 352 on a bloodcomponent type basis. At all times during the apheresis procedure, theflow of whole blood is provided to the blood processing vessel 352through the blood inlet port assembly 416 and is directed to the firststage 312. The control port dam 280 again reduces the potential forblood flowing in a counterclockwise direction in the channel 208.

In the first stage 312, blood is separated into a plurality of layers ofblood component types including, from the radially outermost layer tothe radially innermost layer, RBCs, WBCs, platelets, and plasma. Assuch, the RBCs sediment against the outer channel wall 216 in the firstcell separation stage 312. By configuring the RBC dam 232 such that itis a section of the channel 210 which extends further inwardly towardthe rotational axis 324 of the of the channel housing 204, this allowsthe RBC dam 232 to retain separated red blood cells in the first stage312.

Separated RBCs are removed from the first stage 312 utilizing theabove-noted configuration of the outer channel wall 216, which inducesthe RBCs to flow in a counterclockwise direction (e.g., generallyopposite to the flow of blood through the first cell separation stage312). That is, the portion of the channel 208 proximate the RBC outletport assembly 516 is disposed further from the rotational axis 324 ofthe channel housing 204 than that portion of the channel 210 proximatethe RBC dam 232. As such, separated RBCs flow through the first stage312 in a counterclockwise direction along the outer channel wall 216,past blood inlet port assembly 388 on the blood processing vessel 352,and to an RBC outlet port assembly 516. Since the vertical slot 404 ofthe blood inlet port 392 is substantially parallel with the innerchannel wall 212, the outer channel wall 216, the inner sidewall 372 ofthe blood processing vessel 352 and the outer sidewall 376 of the bloodprocessing vessel 352, it directs the flow of blood in a clockwisedirection in the channel 208 and thus toward the RBC dam 232. Since itis disposed proximate the inner channel wall 212, the introduction ofblood into the blood processing vessel 352 does not substantially affectthe flow of RBCs along the outer channel wall 216. Consequently, RBCseffectively flow undisturbed past the blood inlet port 392 and to theRBC outlet port assembly 516 for removal from the blood processingvessel 352. These RBCs may either be collected and/or provided back tothe donor/patient 4.

Platelets are less dense then RBCs and are thus able to flow beyond theRBC dam 232 and to the platelet collect well 236 in platelet-rich plasmawhere they are removed from the blood processing vessel 352 by theplatelet collect port assembly 416. Again, the blood processing vessel352 via the support 428 and the outer channel wall 216 collectivelydefine the platelet collect well 236 when the blood processing vessel352 is pressurized.

Platelet-poor plasma is less dense than the platelets and continues toflow in a clockwise direction through the second stage 316 to the plasmaoutlet port assembly 452 where at least some of the plasma is removedfrom the blood processing vessel 352. This plasma may be collectedand/or returned to the donor/patient 4. However, some of the plasma flowcontinues in the clockwise direction into and through the third stage320 to the control port assembly 488 to provide for automatic control ofthe location of the interface between the RBCs and platelets in theabove-described manner.

Platelet/RBC Collection

As noted, blood apheresis system 2 provides for contemporaneousseparation of a plurality of blood components during blood processing,including the separation of red blood cells (RBCs), platelets andplasma. In turn, such separated blood components may be selectivelycollected in corresponding storage reservoirs or immediately returned tothe donor/patient 4 during a blood return submode. In this regard, andin one approach where both platelets and RBCs are to be collected, bloodapheresis system 2 may be advantageously employed to collect platelets,and if desired, separated plasma, during a time period(s) separate fromthe collection of red blood cells. In this manner, the collection ofboth high quality platelet units and high quality red blood cell unitscan be realized.

In this regard, the procedures described hereinabove are carried out toprovide priming of extracorporeal tubing circuit 10 and blood processingvessel 352. The initiation of blood processing then provides for thecollection of platelets in reservoir 84 during a first period and thecollection of red blood cells in reservoir 954 during a second period.Plasma collection in reservoir 94 may also be selectively completedduring the first period. During the platelet blood processing period andsuccessive RBC collection procedure, blood component separation device 6will control the initiation and termination of successive blood removaland blood return submodes, as described hereinabove. Additionally, bloodcomponent separation device 6 will control the platelet and RBCcollection processes according to a predetermined protocol, includingcontrol over the divert valve assemblies 1100, 1110 and 1120 of thepump/valve/sensor assembly 1000.

More particularly, following priming, blood separation control device 6provides control signals to pump/valve/sensor assembly 1000 so thatplatelet divert valve assembly 1100 diverts the flow of separatedplatelets pumped through platelet outlet tubing 66 and platelet tubingloop 142 into platelet collection tubing 82 for collection in reservoir84. If plasma collection is desired, blood component separation device 6also provides control signals so that plasma divert valve assembly 1110diverts the flow of separated plasma pumped through plasma outlet tubing68 and plasma tubing loop 162 into plasma collector tubing 92 forcollection in reservoir 94. Additionally, RBC/plasma divert valveassembly 1120 will continue to divert the flow of separated RBCs flowingthrough outlet tubing 64 through return tubing loop 172 and into bloodreturn reservoir 150. When the desired volumes of platelets and plasmahave been collected, blood component separation device 6 willselectively control divert assemblies 1100 and 1110 to divert the flowof platelets and plasma into reservoir 150.

Following completion of platelet and plasma collection, the RBCcollection procedure is initiated via control signals provided by bloodcollection device 6. Such RBC collection procedure includes a setupphase and a collection phase. During the setup phase, the bloodapheresis system 2 is adjusted to establish a predetermined hematocritin those portions of the blood processing vessel 352 and extracorporealtubing circuit 10 through which separated RBCs will pass for collectionduring the RBC collection phase.

More particularly, during the setup phase, and in order to realize apredetermined hematocrit of at least about 75%, a desired packing factorin the first stage 312 of the blood processing vessel 352 isestablished. Additionally, a desired AC ratio (i.e. the ratio betweenthe inlet flow rate to vessel 352 (including whole blood plusanticoagulant AC) and the AC flow rate into tubing circuit 10) will beestablished. Further, the total uncollected plasma flow rate throughblood processing vessel 352 and extracorporeal tubing circuit 10 will beestablished at a predetermined level. These adjustments are carried outin simultaneous fashion to establish the desired hematocrit in anexpeditious manner. As will be appreciated, the adjusted AC ratio andpredetermined hematocrit should be maintained during the subsequent RBCcollection phase.

During the set-up phase, blood component separation device 6 providesappropriate control signals to the pump/valve/sensor assembly 1000 suchthat all separated blood components flowing out of processing vessel 352will pass to return reservoir 150. Also, blood component separationdevice 6 will continue operation of blood inlet pump assembly 1030,including operation during each blood return submode.

In order to establish the desired packing factor, the operating speed ofcentrifuge rotor assembly 568 may be selectively established via controlsignals from blood component separation device 6, and the blood inletflow rate to vessel 352 may be selectively controlled via control byblood component separation device 6 over pump assembly 1030. Moreparticularly, increasing the rpms of centrifuge rotor assembly 568and/or decreasing the inlet flow rate will tend to increase the packingfactor, while decreasing the rpms and increasing the flow rate will tendto decrease the packing factor. As can be appreciated, the blood inletflow rate to vessel 352 is effectively limited by the desired packingfactor.

To establish the desired AC ratio, blood component separation device 6provides appropriate control signals to anticoagulant peristaltic pump1020 so as to introduce anticoagulant into the blood inlet flow at apredetermined rate, as previously described hereinabove. Relatedly, inthis regard, it should be noted that the inlet flow rate ofanti-coagulated blood-to-blood processing vessel 352 is limited by apredetermined, maximum acceptable anticoagulant infusion rate (ACIR) tothe donor/patient 4. As will be appreciated by those skilled in the art,the predetermined ACIR may be established on a donor/patient-specificbasis (e.g. to account for the particular total blood volume of thedonor/patient 4).

To establish the desired total uncollected plasma flow rate out of bloodprocessing vessel 352, blood collection device 6 provides appropriatecontrol signals to plasma pump assembly 1060 and platelet pump assembly1040. Relative to platelet collection, such control signals willtypically serve to increase plasma flow through plasma outlet port 456,and thereby reduce plasma flow with RBCs through RBC outlet port 520.This serves to increase the hematocrit in the separated RBCs.Additionally, it is preferable for blood processing device 6 to providecontrol signals to platelet pump assembly 1040 so as to establish apredetermined flow rate wherein platelets and some plasma pass togetherthrough platelet port 420, thereby reducing platelet clumping downstreamin tubing circuit 10. In this regard, such predetermined rate will belimited by the diameter of the platelet outlet tubing 66 and the size ofthe internal channels (e.g. 140 a, 140 b) within molded cassette 110.

In one embodiment, where centrifuge rotor assembly 568 defines a rotordiameter of about 10 inches, and where a blood processing vessel 352 isutilized, as described hereinabove, it has been determined that channelhousing 204 can be typically driven at a rotational velocity of about3000 rpms to achieve the desired hematocrit during the setup and bloodcollection phases. Correspondingly, the blood inlet flow rate to vessel352 should be established at below about 64.7 ml/min. The desiredhematocrit can be reliably stabilized by passing about two whole bloodvolumes of reservoir 352 through reservoir 352 before the RBC collectionphase is initiated.

To initiate the RBC collection phase, blood component separation device6 provides an appropriate control signal to RBC/plasma divert valveassembly 1120 so as to direct the flow of RBCs removed from bloodprocessing vessel 352 into RBC collection reservoir 954. Both theplatelet divert valve assembly 1100 and plasma divert valve assembly1110 remain in a position to direct flow into reservoir 150 for returnto donor/patient 4 during blood return submodes. In the later regard, itis preferable that, during blood return submodes of the RBC collectionphase, blood collection device 6 provide appropriate control signals soas to stop the operation of all pump assemblies other than return pumpassembly 1090. In this regard, stoppage of inlet pump assembly 1030avoids recirculation of uncollected blood components into vessel 352 andresultant dilution of separated RBC components within vessel 352.

As will be appreciated, in the present invention separated RBCs are notpumped out of vessel 352 for collection, but instead are pushed outvessel 352 and through extracorporeal tubing circuit 10 by the pressureof the blood inlet flow to vessel 352. Consequently, trauma to thecollected RBCs is minimized.

During the RBC collection phase, the inlet flow into vessel 352 islimited by the above-noted maximum, acceptable ACIR to the donor/patient4. The desired inlet flow rate is also limited by that necessary tomaintain the desired packing factor, as also discussed. In this regard,it will be appreciated that, relative to the setup phase, the inlet flowrate may be adjusted slightly upwards during the RBC collection phasesince not all anticoagulant is being returned to the donor/patient 4.That is, a small portion of the AC remains with the plasma that iscollected with the RBCs in RBC reservoir 954.

Following collection of the desired quantity of red blood cells, bloodseparation device 6 may provide a control signal to divert assembly1120, so as to divert RBC flow to reservoir 150. Additionally, iffurther blood processing by apheresis is not desired, rinsebackprocedures may be completed. Additionally, the red blood cell reservoir954 may be disconnected from the extracorporeal tubing circuit 10. Astorage solution may then be added to the red blood cell reservoir orbag 954 preferably through the opening of optional frangible connector968. Such storage solution may advantageously facilitate storage of theRBCs for up to about 42 days at a temperature of about 1-6 C.

While one approach for platelet and RBC collection has been describedabove, other approaches will be apparent. By way of primary example, thedescribed RBC collection procedure may be carried out following bloodpriming, and prior to platelet collection. Such an approach wouldadvantageously allow RBC collection to occur in the course of ACramping, thereby reducing total processing time requirements. That is,since AC ramping up to a predetermined level is typically, graduallycompleted prior to the start of a platelet collection procedure (e.g. soas to maintain an acceptable ACIR), completing RBC collection proceduresin the course of AC ramping would reduce the overall processing time forRBC and platelet collection.

Further, and as noted above, plasma collection could occurcontemporaneous with RBC collection. Additionally, in this regard,plasma collection could occur during both platelet and RBC collectionprocedures, depending upon the volume of plasma product desired.Finally, it has been recognized that the present invention may also beemployable to simultaneously separate and collect both red blood cellsand platelets, and if desired, plasma.

Graphical Computer Interface

In order to assist an operator in performing the various steps of theprotocol being used in an apheresis procedure with the apheresis system2, the apheresis system 2 further preferably includes a computergraphical interface 660 as illustrated in FIG. 1. The followingdescription describes an interface for use by an Englishlanguage-speaking operator. For other operations and/or languages, thetextual portions of the interface would, of course, be adaptedaccordingly. The graphical interface 660 includes a computer display 664that has “touch screen” capabilities. Other appropriate input devices(e.g., keyboard) may also be utilized alone or in combination the touchscreen. For example, a pump pause and a centrifuge stop button of thewell-known membrane type may be provided. The graphics interface 660 notonly allows the operator to provide the necessary input to the apheresissystem 2 such that the parameters associated with operation of theapheresis system may be determined (e.g., data entry to allowdetermination of various control parameters associated with theoperation of the apheresis system 2), but the interface 660 may alsoassist the operator by providing pictorials of certain steps of theapheresis procedure. Moreover, the interface 660 may also effectivelyconvey the status of the apheresis procedure to the operator.Furthermore, the interface 660 also may be used to activate standardizedcorrective actions (i.e., such that the operator need only identify theproblem and indicate the same to the interface 660 which will thendirect the apheresis system 2 to correct the same). Descriptions andprocedures for various of these features as presently preferred inutilizing an interface like interface 660 may be found in U.S. Pat. Nos.5,653,887 and 5,941,842, inter alia.

Even so, some alternative applications of an interface such as interface660 with the alternative embodiments of the present invention will nowbe described. These applications may likely be considered relative tothe corrective actions described briefly above. In particular, and firstreferring to FIG. 7, at the start of an apheresis procedure a masterscreen 696 is displayed to the operator on the display 664. The masterscreen 696, as well as each of the screens displayed to the operator bythe interface 600, includes a status bar 676. The status bar 676preferably includes various icons representing various steps in theoverall apheresis procedure as described in more detail in theabove-referenced U.S. patents. The status bar 676 preferably alsoincludes a status line area 712. Such a status line area 712 providesfor textually conveying status messages to the operator concerningcertain phases of the operation of the blood component separation device6.

The master screen 696, as well all other screens displayed to theoperator by the interface 660 during an apheresis procedure, alsoinclude a work area 688. The work area 688 provides multiple functions.Initially, the work area 688 displays additional information(pictorially and textually in some instances) on performing theapheresis procedure to the operator (e.g., certain additional substepsof the apheresis procedure, and/or addressing certain “conditions”encountered during the apheresis procedure). Moreover, the work area 688also displays additional information on the status of the apheresisprocedure to the operator. Furthermore, the work area 688 also providesfor operator interaction with the computer interface 660, such as byallowing/requiring the operator to input certain information. Touchscreen capabilities are preferable here.

In the event that the operator requires additional guidance with regardto any of the steps presented on a procedure or status screen, theoperator may touch the help button 692 which may be provided on anyscreen. This may then display a menu of screens (not shown), which theoperator may view and/or may sequentially present a number of helpscreens (not shown) associated with the particular screen. Moreover, thehelp screen may provide the operator with more detail, in the nature ofadditional pictorials and/or text, regarding one or more aspects of theparticular procedure or operational status of interest. Various of theincluded screens in the graphics interface 660 may include a help button692 to provide this help feature.

Once the operator completes all of the donor/patient prep steps and hasfully initiated the blood flow and separation procedure (as may be aidedby a series of screens not shown here; see the above-referenced U.S.patents), a run screen such as the screen 844 illustrated in FIG. 8 maybe displayed. The run screen 844 may primarily display information tothe operator regarding the apheresis procedure. For example, the runscreen 844 shown in FIG. 8 includes a blood pressure display 848 (i.e.,to convey to the operator the donor/patient's extracorporeal bloodpressure), a platelet collect display 852 (i.e., to convey to theoperator an estimate of the number of platelets which have beencurrently collected), a plasma collect display 856 (i.e., to convey tothe operator the amount of plasma which has been currently collected),and a time display 860 (e.g., both the amount of time which has lapsedsince the start of the collection procedure (the left bar graph andnoted time), as well as the amount of time remaining in the collectionprocedure (the right bar graph and noted time). A control button (notshown) may be provided to toggle between the time remaining display andthe start and stop time display.

The run screen 844 may also display, in the case of a single needleprocedure (i.e., where only one needle is utilized to fluidlyinterconnect the donor/patient 4 with the blood component separationdevice 6), whether blood is being withdrawn from the donor/patient 4(e.g., by displaying text such as “draw in progress” in the status linearea 712) or is being returned to the donor/patient 4 (e.g., bydisplaying the textual phrase “return in progress” as shown in thestatus line area 712 in FIG. 8). This information may be useful to thedonor/patient 4 in that if the donor/patient 4 is attempting to maintaina certain blood pressure by squeezing an article to assist in removal ofblood from the donor/patient 4, the donor/patient 4 will be providedwith an indication to suspend these actions while blood is beingreturned to the donor/patient 4.

During the apheresis procedure, certain conditions may be detected bythe apheresis system 2 which would benefit from intervention and/orinvestigation by the donor/patient or the operator. If one of thesetypes of conditions is detected, appropriate warning and/or alarmscreens may be displayed to the operator. One embodiment of a warningscreen 864 is illustrated in FIG. 9. Initially, the warning screen 864textually conveys a potential problem with the system 2 via the textualmessage displayed in the status line area 712. As shown in FIG. 9, thewarning depicted in the presently displayed embodiment is that the drawpressure is too low. This warning would be indicated when the pressurelevel has been reached as calculated or set in whichever alternativeembodiment is being used as described above. The text may be useful inensuring that the operator understands the problem. Other warning soundsor flashing lights may also be emitted and/or displayed by theseparation device 6 whether as a part of the display screen 660 orseparately. The warning screen 864 also preferably includes an actionpictorial 872, which graphically conveys to the operator the action,which should be taken in relation to the problem. These are actions thatmay be difficult or impossible for the system 2 to take itself. In thepresent example, a squeeze icon is displayed to convey that thedonor/patient should squeeze his or her fist in order to raise theaccess/draw pressure.

If the access/draw pressure does not resolve (by any of the pre-selectedmethods as described above), then a regular/full alarm may be indicatedas shown by the screen 878 in FIG. 10. In FIG. 10, a textual message“draw pressure too low” is displayed in the textual line area 712, andfurther text (in area 914) is displayed in the work area 688representing various alternative system elements and/or functions, whichshould be inspected by the operator to ensure proper system operation. Apictorial representation 912 of the system elements and/or functions isalso displayed in the work area 688. Finally, the alarm screen 878preferably includes an inspection results array 876, which allows theoperator to indicate the results or a desired next operational procedureas a result of the inspection. In the illustrated embodiment, the array876 includes a continue button 906, a rinseback button 908, an end runbutton 909 and an adjust button 910. These are preferablytouch-activated buttons for use on a touch sensitive screen 664.

Depending upon the selection made by the operator on the inspectionresults array 876, additional questions may be posed to the operator infurther screens, which require further investigation and/or whichspecify the desired remedial action. For example, the adjust button 910can take the operator to another screen (not shown) to adjust the flowrate or rates for this particular donor/patient. The alarm screen 878includes a remedial action pictorial 912 and remedial action text 914 toconvey to the operator how to correct the identified problem.

The computer interface 660 may also allow the operator to initiate sometype of corrective action based upon observations made by and/orconveyed to the operator. For instance, various screens of the interface660 may include a trouble-shooting button (not shown), a preferredembodiment of which is described in the above-referenced U.S. patents.Flow rate adjustments may also (alternatively and/or additionally) bemade available through trouble shooting buttons such as these.

The foregoing description of the present invention has been presentedfor purposes of illustration and description. Furthermore, thedescription is not intended to limit the invention to the form disclosedherein. Consequently, variations and modifications commensurate with theabove teachings, and skill and knowledge of the relevant art, are withinthe scope of the present invention. The embodiments describedhereinabove are further intended to explain best modes known ofpracticing the invention and to enable others skilled in the art toutilize the invention in such, or other embodiments and with variousmodifications required by the particular application(s) or use(s) of thepresent invention. It is intended that the appended claims be construedto include alternative embodiments to the extent permitted by the priorart.

1. A method for controlling an extracorporeal blood processing system,comprising an extracorporeal blood circuit, in response to fluidpressure changes in a fluid flow in the extracorporeal blood circuit,the method comprising the steps of: sensing a fluid pressure in theextracorporeal blood circuit; comparing the fluid pressure to athreshold value; stopping fluid flow, when the fluid pressure is belowthe threshold value; and resuming fluid flow, when the fluid pressurerises to a set point within a selected period of time.
 2. A methodaccording to claim 1, wherein the set point is the threshold value.
 3. Amethod according to claim 1, further comprising the step of setting afull alarm condition when the fluid pressure being sensed does not riseabove the set point within a selected period of time.
 4. A methodaccording to claim 3, in which the step of setting a full alarmcondition comprises complete stoppage of fluid flow in theextracorporeal blood circuit.
 5. A method according to claim 1, furthercomprising the step of emitting a warning alarm signal contemporaneouslywith said step of stopping fluid flow.
 6. A method according to claim 5,in which said warning alarm signal is an audible squeeze beep sound. 7.A method according to claim 1, further comprising the steps of:interpreting a particular quantity of fluid pressure comparisons wherethe fluid pressure is below the threshold value occurring within aparticular time period; and signaling an alarm.
 8. A method according toclaim 7, in which the particular quantity of fluid pressure comparisonsis set to be three and the particular time period is set to be threeminutes.
 9. A method according to claim 1, in which the threshold valueis adjustable in view of certain pre-selected parameters including fluidflow rate and fluid viscosity.
 10. A method according to claim 9,wherein the extracorporeal blood circuit has an inlet tubing for fluidflow, and a needle for fluid flow into the inlet tubing, and thethreshold value is:Draw Threshold Value=Config+75−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the inlet tubing line; H_(in)=Hematocritin the inlet tubing line; Q_(n)=fluid flow rate in the needle; andH_(n)=Hematocrit in the needle.
 11. A method according to claim 9,wherein the extracorporeal blood circuit has an inlet tubing for fluidflow, and a needle for fluid flow into the inlet tubing; and thethreshold value is:Draw Threshold Value=Config+75−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the inlet tubing line; H_(in)=Hematocritin the inlet tubing line; Q_(n)=fluid flow rate in the needle; andH_(n)=Hematocrit in the needle.
 12. A method according to claim 1,wherein the extracorporeal blood circuit has a return tubing for fluidflow, and the method further comprises: sensing return fluid pressure;and comparing the return fluid pressure to the return threshold valuethat is adjustable in view of certain pre-selected parameters includingfluid flow rate and fluid viscosity.
 13. A method according to claim 12,wherein the extracorporeal blood circuit has a needle for fluid flowfrom the return tubing, and the return threshold value is:Return Threshold Value=Config−50−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the return tubing line;H_(in)=Hematocrit in the return tubing line; Q_(n)=fluid flow rate inthe needle; and H_(n)=Hematocrit in the needle.
 14. A method accordingto claim 12, wherein the extracorporeal blood circuit has a needle forfluid flow from the return tubing, and the return threshold value is:Return Threshold Value=Config−50−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the return tubing line;H_(in)=Hematocrit in the return tubing line; Q_(n)=fluid flow rate inthe needle; and H_(n)=Hematocrit in the needle.
 15. A method accordingto claim 1, wherein the extracorporeal blood processing system is asingle needle blood separation system in which blood is drawn from adonor/patient, separated blood components are first accumulated in areservoir, and the accumulated components are then cyclically pumped outof the reservoir back to the donor/patient, the method comprising thestep of pumping the accumulated fluid components out of the reservoirsimultaneously with stopping fluid flow.
 16. A method according to claim15, in which the blood is alternately drawn and returned in a cycle, andin which the step of pumping the accumulated fluid components out of thereservoir is conditioned upon the draw cycle being greater than apre-selected percentage of completion.
 17. A method according to claim16, in which the percentage of completion is set at 90%.
 18. A methodaccording claim 1, in which the e set point is −50 mmHg.
 19. Anextracorporeal blood processing apparatus adapted to cooperate with anextracorporeal blood circuit, comprising: a fluid pressure-monitoringdevice for sensing a pressure in an extracorporeal blood circuit; atleast one fluid flow control device for circulating at least one liquidin the extracorporeal blood circuit; and a control device for receivinga pressure signal from the pressure monitoring device and comparing itto a threshold value, and for causing the operation of the at least oneflow control device, wherein the control device is programmed for:stopping the at least one fluid flow control device, when the fluidpressure sensed by the fluid pressure monitoring device is below thethreshold value; and resuming the operation of the at least one flowcontrol device, when the fluid pressure sensed by the fluid pressuremonitoring device rises above a set point within a selected period oftime.
 20. An apparatus according to claim 19, wherein the set point isthe threshold value.
 21. An apparatus according to claim 19, wherein thecontrol device is further programmed for setting a full alarm conditionwhen the fluid pressure sensed by the fluid pressure monitoring devicedoes not rise above the set point within a selected period of time. 22.An apparatus according to claim 21, in which the control device isprogrammed for stopping the operation of the at least one flow controldevice when setting a full alarm condition.
 23. An apparatus accordingto claim 19, wherein the control device is further programmed forcausing a warning alarm signal to be emitted when pausing the at leastone fluid flow control device.
 24. An apparatus according to claim 19,wherein the control device is further programmed for: interpreting aparticular quantity of fluid pressure comparisons where the fluidpressure is below the threshold value occurring within a particular timeperiod; and signaling an alarm.
 25. An apparatus according to claim 24,in which the particular quantity of fluid pressure comparisons is set tobe three and the particular time periods set to be three minutes.
 26. Anapparatus according to claim 19, in which the threshold value isadjustable in view of certain pre-selected parameters including fluidflow rate and fluid viscosity.
 27. An apparatus according to claim 26,adapted for cooperating with an extracorporeal blood circuit having aninlet tubing for fluid flow, and a needle for fluid flow into the inlettubing, and the threshold value is:Draw Threshold Value=Config+75−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the inlet tubing line; H_(in)=Hematocritin the inlet tubing line; Q_(n)=fluid flow rate in the needle; andH_(n)=Hematocrit in the needle.
 28. An apparatus according to claim 26,adapted for cooperating with an extracorporeal blood circuit having aninlet tubing for fluid flow, and a needle for fluid flow into the inlettubing, and the threshold value is:Draw Threshold Value=Config+75−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the inlet tubing line; H_(in)=Hematocritin the inlet tubing line; Q_(n)=fluid flow rate in the needle; andH_(n)=Hematocrit in the needle.
 29. An apparatus according to claim 19,adapted for cooperating with an extracorporeal blood circuit having areturn tubing for fluid flow, wherein the fluid pressure monitoringdevice is adapted for sensing a return fluid pressure and the controldevice is programmed for comparing the return fluid pressure to a returnthreshold value that is adjustable in view of certain pre-selectedparameters including fluid flow rate and fluid viscosity.
 30. Anapparatus according to claim 29, wherein the return threshold value is:Return Threshold Value=Config−50−0.3309*Q _(in)/(1−H _(in))−0.3026*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the return tubing line;H_(in)=Hematocrit in the return tubing line; Q_(n)=fluid flow rate inthe needle; and H_(n)=Hematocrit in the needle.
 31. An apparatusaccording to claim 29, wherein the return threshold value is:Return Threshold Value=Config−50−0.3309*Q _(in)/(1−H _(in))−0.5602*Q_(n)/(1−H _(n)) where, Config=a configuration pre-selected pressurevalue Q_(in)=fluid flow rate in the return tubing line;H_(in)=Hematocrit in the return tubing line; Q_(n)=fluid flow rate inthe needle; and H_(n)=Hematocrit in the needle.
 32. The apparatusaccording to claim 19, for cooperating with an extracorporeal bloodcircuit having a reservoir for storing separated blood components to becyclically pumped out of the reservoir back to a donor/patient, wherein:the at least one fluid flow control device comprises a blood inlet pumpand a blood return pump; and the control device is further programmedfor simultaneously causing the blood return pump to pump the accumulatedfluid components out of the reservoir and the blood inlet pump to pause,when the fluid pressure sensed by the fluid pressure monitoring deviceis below the threshold value.
 33. An apparatus according to claim 32, inwhich the control device is programmed for causing blood to bealternately drawn by the blood inlet pump and returned by the bloodreturn pump in a cycle, and for causing the blood return pump to pumpthe accumulated fluid components out of the reservoir depending upon thedraw cycle being greater than a pre-selected percentage of completion.